Complete Overview of 2025 CPT Codes for Genetic Testing

Genetic testing is essential for diagnosing hereditary conditions, informing treatment choices, and forecasting disease risks. As technology progresses, it is imperative that medical billing and coding evolve accordingly. The updates to the CPT codes for 2025 introduce a number of new codes related to genetic testing, which will affect medical practices, laboratories, and insurance reimbursement processes.

For those involved in medical coding, billing, or revenue cycle management, it is vital to comprehend these updates to ensure accurate claims submission and adherence to compliance standards. This guide provides an overview of the new 2025 CPT codes for genetic testing, along with billing guidelines and reimbursement strategies.

Overview of 2025 CPT Code Changes for Genetic Testing

Current Procedural Terminology (CPT) codes are utilized in medical billing to document diagnostic procedures, including genetic tests. The CPT codes for genetic testing are categorized into three primary groups:

• Tier 1 Molecular Pathology Codes: Standardized tests for frequently analyzed genes, such as BRCA1/BRCA2.
• Tier 2 Molecular Pathology CPT Codes: Applicable to less common genetic markers and panel-based tests.
• Proprietary Laboratory Analyses (PLA) Codes: Specific genetic tests conducted by individual laboratories.
• Genomic Sequencing Procedure (GSP) Codes: Codes designated for next-generation sequencing (NGS) and panel-based genomic testing.

Each year, the CPT code set undergoes updates to incorporate advancements in medical services. The 2025 CPT code update features new codes for genetic and molecular testing, particularly in:

• Proprietary Laboratory Analyses (PLA) Codes
• Molecular Diagnostics
• Hereditary Testing

These updates assist healthcare providers in billing accurately for genetic testing services, leading to quicker reimbursements and a reduction in claim denials.

2025 Optimized CPT Coding Guide for Molecular Pathology

The American Medical Association (AMA) has implemented 420 updates to the CPT code set, which includes 270 new codes, 112 deletions, and 38 revisions. Importantly, 37% of the newly introduced codes are related to proprietary laboratory analyses, with a primary emphasis on innovative genetic testing.

Billing Protocols for Medicare Coverage and Molecular Pathology Procedures

The updates to the CPT coding for 2025 include changes in molecular testing, sequencing, and risk assessment. Below is a detailed breakdown:

Medicare Billing for Non-Covered Services

It is inappropriate to bill Medicare for services that are not covered as if they are covered. When submitting claims for services that do not qualify for coverage, it is essential to apply the correct modifier.

Gene-Specific Code Selection

The selection of codes is contingent upon the specific gene(s) being analyzed. Codes for gene variant testing utilize common variant names. Although the variants listed are generally included in the test, this list is not comprehensive. Any additional variants of the same gene that are part of the analysis should be considered part of the procedure and must not be reported separately.

Full gene sequencing should not be reported using codes specific to variants unless the CPT code explicitly states “full gene sequence” in its description.

Tier 1 and Tier 2 Molecular Pathology Codes

• Tier 1 codes pertain to tests for a specific gene or Human Leukocyte Antigen (HLA) locus.
• Tier 2 codes (81400-81408) encompass molecular pathology procedures not included in Tier 1 and generally represent testing for lower-volume or rare diseases. These codes should only be utilized when necessary and in accordance with coding and billing policies.

If a claim encompasses the following Tier 2 codes, it is imperative to provide additional information in the claim narrative to identify the gene(s) that were analyzed. Failing to do so may lead to the rejection of the claim:

• 81400
• 81401
• 81402
• 81403
• 81404
• 81405
• 81406
• 81407
• 81408
• 81479 (Unlisted Molecular Pathology)

Reporting Unlisted Molecular Pathology Code (81479)

Providers are required to utilize the procedure code that most accurately describes the service performed. In instances where no Tier 1 or Tier 2 code suitably represents the analyte tested, the unlisted molecular pathology code (81479) should be employed.

When billing for 81479, it is essential to specify the gene being tested in:

• Block 80 (Part A for UB-04 claims)
• Box 19 (Part B for paper claims)
• Electronic equivalent fields for digital claims

Omission of this information will lead to claims being returned or denied. Additionally, medical records may be requested to confirm the analytic validity, clinical utility, and justification for the use of 81479.

Documentation for Multiple Procedure Codes

In cases where multiple procedure codes are submitted on a claim (whether they are standard or unlisted), the documentation must clearly substantiate each code. If the documentation does not align with the billed codes, the services may be denied in accordance with Title XVIII of the Social Security Act, Section 1833.

Testing for Multiple Genes & Next-Generation Sequencing (NGS)

Testing a panel of genes is distinct from testing individual genes separately. Claims must be medically justified:

• If billing for a panel, medical records must validate its necessity.

Genes tested on the same date of service are classified as:

• Parallel Testing: This occurs when multiple genes are analyzed simultaneously for the same indication without one result affecting another.
• Serial Testing: This refers to gene analysis conducted in sequence, where subsequent tests rely on earlier results.

If NGS technology is employed and several genes are assessed simultaneously, they are regarded as components of a unified panel, in accordance with the NCCI Manual (Chapter 10, Section F, Number 8). Conversely, if genes are evaluated sequentially, claims must be filed separately for each gene. The order from the treating clinician must indicate whether a panel or individual genes were requested, and documentation should substantiate the medical necessity of the billed service.

Medicare policy prohibits separate reimbursement for various testing methods applied to the same analyte.

Generally, billing for multiple distinct genetic tests for a single patient on the same date is not anticipated. In exceptional circumstances where more than one test is deemed medically necessary, providers are required to validate each as a distinct procedural service utilizing modifier -59.

Modifier -59: Distinct Procedural Service

Modifier -59 is utilized to signify that a procedure is independent from others conducted on the same day, applicable to radiology, surgical, or medical services when suitable.

Billing guidelines for Modifier -59:

• The initial reported code is billed without a modifier.
• Additional codes are billed on separate lines with the modifier.
• Documentation must validate a different session, procedure, site, system, incision, lesion, or injury from other services rendered on the same day.

If another, more precise modifier is available, it should be utilized in place of -59. The application of this modifier indicates that a service is distinct rather than part of a panel and may prompt a request for medical records. Frequent application of modifier -59 may result in medical review.

Genomic Sequencing Profiles (GSP)

When a genomic sequencing test encompasses genes categorized under multiple code descriptors, the most specific code for the primary disorder should be reported. Submitting various codes for the same gene will lead to claim rejection or denial.

Multianalyte Assays utilizing Algorithmic Analyses (MAAAs) and Proprietary Laboratory Analyses (PLAs)

If a valid PLA code is available, it should be utilized in place of a Tier 1 or Tier 2 code. The submission of both a PLA and a Tier 1/Tier 2 code is deemed incorrect coding and may lead to claim denial.

MAAA component procedures must not be billed separately. Claims that include additional codes for MAAA inputs will be rejected.

• PLA and MAAA codes can be found in Appendix O of the CPT Manual.
• In the absence of a specific code, the unlisted MAAA procedure code (81599) should be employed.
• When billing 81599, a concise description of the analysis, not exceeding 80 characters, must be provided in:
• Block 80 (Part A UB-04 claims)
• Box 19 (Part B paper claims)
• The corresponding electronic field for digital claims

Claims that lack this information will be returned or denied. Medical records may also be requested to confirm the validity and necessity of the test.

Date of Service (DOS)

For clinical laboratory tests and pathology services, the DOS is generally the date on which the specimen was collected. If the collection occurs over two calendar days, the DOS is the date on which the collection concluded. There are exceptions to DOS policies, as detailed in CMS IOM Publication 100-04, Chapter 16, Section 40.8.

Documentation Requirements

All medical records must be:

• Legible and contain patient identification information (name, DOS, etc.)
• Supportive of the reported ICD-10-CM and CPT/HCPCS codes

According to CFR Section 410.32, the medical record must illustrate that testing impacts treatment and is essential for managing the patient’s condition.

Ordering documentation from physicians or non-physician practitioners (NPP) must encompass:

• Relevant medical history, findings from physical examinations, and the rationale for diagnostics
• Proof of a minimum of two evaluation and management (E/M) visits within the preceding six months
• Test orders that distinctly outline the analyses requested

Laboratories conducting tests are required to keep records that include:

• Their accreditation status
• Test requisition forms
• Records of procedures performed
• Documentation of quality control measures

Inadequate documentation may lead to the denial of claims or requests for further records.

The Bottom Line

The updates to the 2025 CPT codes concerning genetic testing present new billing opportunities and challenges for healthcare providers and laboratories. Staying informed about molecular pathology, genomic sequencing, and proprietary test codes is essential for achieving accurate reimbursement. A thorough understanding of payer policies, compliance requirements, and best practices in billing will facilitate the claims process and mitigate revenue loss. For a seamless transition, it is advisable to seek guidance from coding experts and medical billing professionals who focus on reimbursement for genetic testing.

Frequently Asked Questions

Q1. How many genes does CPT code 81408 test for?

CPT code 81408 relates to molecular pathology procedures that involve the examination of specific genes linked to particular conditions. The precise number of genes assessed under this code may differ, as it encompasses tests for rare genetic disorders. For accurate details, it is crucial to refer to the most recent CPT code descriptions or pertinent medical billing resources.

Q2. What do molecular pathology procedure level numbers indicate?

Molecular pathology procedure codes are classified into various tiers to represent the complexity and resources necessary for the tests:

• Tier 1 Codes (e.g., 81200-81383): These codes signify well-established tests for common genetic variants.
• Tier 2 Codes (e.g., 81400-81408): These codes are segmented into levels based on the technical and interpretive effort required, with higher levels denoting more intricate analyses.

Each level within Tier 2 corresponds to specific procedures and the complexity associated with the testing process.

Q3. What is CPT code 81479?

CPT code 81479 is assigned to “Unlisted molecular pathology procedures.” It is utilized when a molecular pathology test lacks a specific CPT code. This code guarantees that unique or less common genetic tests are billed correctly, even when a designated code is not available.

Q4. What is the CPT code for GeneSight testing?

GeneSight Psychotropic testing is denoted by CPT code 0345U. This proprietary laboratory analysis assesses how a patient’s genetic profile may influence their response to certain psychotropic medications, evaluating multiple genes to inform treatment decisions.

Q5. What are the CPT codes for genetic testing?

Genetic testing includes a variety of CPT codes, each linked to specific tests:

• 81200-81383: Molecular pathology procedures for particular gene analyses.
• 81400-81408: Tier 2 molecular pathology procedures, classified by complexity.
• 81410-81471: Genomic sequencing procedures and other molecular multianalyte assays.
• 81479: Unlisted molecular pathology procedures.

These codes enable precise billing and documentation of different genetic tests.

Q6. What are pathology CPT codes?

Pathology CPT codes range from 80047 to 89398 and encompass a wide array of laboratory procedures:

• 80047-80076: Organ or disease-oriented panels
• 80150-80299: Therapeutic drug assays
• 81200-81479: Molecular pathology procedures, which include genetic testing
• 88300-88399: Surgical pathology
• 89250-89398: Reproductive medicine and cytogenetics

These codes are crucial for billing pathology and laboratory tests, ensuring accurate reimbursement.

Q7. What is genotype testing, and what CPT codes are used for it?

Genotype testing identifies an individual’s genetic sequence variations, aiding in the assessment of risks for hereditary diseases and responses to medications. Common CPT codes for genotype testing are:

• 81225-81227: CYP2C19, CYP2D6, and other pharmacogenetic testing
• 81291: JAK2 gene testing (applicable in hematologic disorders)
• 81479: Utilized for unlisted genetic tests when no specific CPT code is available

Pro Tip:

Before billing for genotype tests, confirm whether the payer mandates prior authorization, as many insurers enforce strict coverage policies for genetic testing.

Q8. What is the CMS 14-day rule?

The CMS 14-Day Rule, also referred to as the Date of Service (DOS) Policy, is a regulation set forth by the Centers for Medicare and Medicaid Services (CMS) to guarantee the timely submission of claims for clinical diagnostic laboratory tests.