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    v1.0.30
    OpenPayerBilling CodesGenetic Analysis ProceduresCPT cpt-81301-microsatellite-instability-msi-testing
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    CPT 81301: Microsatellite Instability (MSI) Testing in Tumor Tissue

    CPT code 81301 describes a laboratory molecular diagnostic test that detects microsatellite instability (MSI) in tumor tissue, used to evaluate genomic instability in cancers such as colorectal carcinoma; the service is a technical laboratory pathology test performed on tumor tissue specimens, typically provided in an anatomic pathology or molecular diagnostics laboratory (hospital or independent clinical lab) from surgical or biopsy tissue samples.

    For related coverage guidance, see recent payer policy updates: Oral Cancer Screening and Testing, RTM Testing for Alpha-1 Antitrypsin Deficiency, Cytochrome P450 Genotype-Guided Treatment Strategy Corporate Medical Policy.

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    Clinical & Coding Specifications

    Clinical Context

    A 62-year-old patient with a recently resected stage II colon adenocarcinoma undergoes tumor testing to evaluate microsatellite instability (MSI) status. Formalin-fixed, paraffin-embedded tumor tissue from the surgical specimen is submitted to the molecular pathology laboratory. The lab technician performs the 81301 assay to detect MSI in tumor cells, which informs prognosis and eligibility for further germline testing for Lynch syndrome or consideration of immune checkpoint inhibitor therapy. The clinical workflow includes: specimen accessioning and verification, selection of representative tumor block, DNA extraction, PCR-based or next-generation sequencing MSI analysis, analytic interpretation by a molecular pathologist, and reporting of MSI-high, MSI-low, or microsatellite stable results back to the treating surgical oncologist or medical oncologist. Associated documentation in the chart includes pathology accession numbers, tumor percentage, test method, and test report with implications for genetic counseling referral when MSI-high is detected.

    Related CPT Codes

    CPT CodeDescriptionRelationship to This Procedure
    88305Level IV pathology examination, surgical pathology, gross and microscopic examinationPerformed on the resected colon specimen prior to MSI testing; pathology report provides specimen selection and tumor percentage.
    81292BRAF (e.g., V600E) mutation analysis by molecular techniqueOften performed alongside MSI testing to help distinguish sporadic MSI-high tumors from Lynch syndrome when negative for BRAF V600E indicates potential hereditary disease.
    81445Oncology (colorectal) multigene panel, analysis by NGS (interpretation may vary)May be ordered in conjunction with MSI testing for broader somatic or germline mutation profiling.
    88342Cytopathology, gross and microscopic examination with cell blockIf small biopsy or cytology material is used for MSI testing, this code documents processing of cell block material.
    80500Quantitative analysis for nucleic acid amplification (e.g., real-time PCR)Method-related billing that can be reported when specific instrument-based quantitative assays are used in the MSI testing workflow.

    Related Modifiers

    8 rows

    ModifierDescriptionWhen to Use
    26Modifier 26 (Professional Component) identifies and bills only the professional portion of a split service — the physician’s interpretation, report, and medical judgment — when the technical…- Use CPT Modifier -26 when you are billing only the professional component (PC) of a split‑bill eligible service—i.e., you performed the physician interpretation, medical judgment and prepared a…
    90Modifier ‑90 (Reference/Outside Laboratory) indicates that a laboratory test was performed by an entity other than the treating or reporting provider. The American Medical Association defines…- Use CPT modifier -90 when a laboratory test is performed by an outside/reference laboratory (an entity other than the treating or reporting physician or qualified professional) and the claim needs…
    59Modifier 59 indicates a distinct procedural service when two procedures that are not normally billed together are clinically and procedurally separate. The CPT definition (as reiterated by CMS)…- Use modifier -59 to report a distinct procedural service when documentation supports that the procedure reported is not normally billed together with another service on the same day because of a…
    62Modifier 62 indicates that two surgeons function as co‑surgeons, each performing distinct parts of the same primary surgical procedure. It is appended to the primary procedure code (and any…- Use modifier -62 when two surgeons act as co‑surgeons (both primary surgeons) on a single definitive primary procedure, each performing distinct parts of the same surgical procedure (append -62 to…
    78CPT modifier -78 indicates an unplanned, related return to the operating or procedure room by the same provider during the global postoperative period. It is appended when treatment for a…- Use modifier -78 when an unplanned, related complication during the original procedure’s global postoperative period requires the patient to return to a formal operating or procedure room and the…
    80CPT® Modifier 80 (Assistant Surgeon) is appended to a surgical CPT code when a physician (MD or DO) provides full, continuous assistance throughout the operative procedure. It is intended only for…- Use CPT Modifier -80 when a physician (MD or DO) serves as an assistant surgeon and provides full, continuous assistance throughout the entire operative procedure; append -80 to the surgical CPT…
    22Modifier –22 (Increased Procedural Services) is used when a reported procedure is substantially more extensive than normally required. The CPT Manual and CMS state it may be appended only when the…- When to use: Append modifier -22 to a procedural CPT code when the service performed is substantially more extensive than the usual service described by that code — i.e., the procedure required…
    52Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…

    Related Provider Taxonomies

    8 rows

    Taxonomy Code
    208000000X
    207RP1001X
    208M00000X
    207L00000X
    363L00000X
    261QS1000X
    2080C0008X
    2080S0010X

    Related ICD-10-CM Codes

    28 rows

    ICD-10-CM CodeDescription
    C16.9Malignant neoplasm of stomach, unspecified
    C17.9Malignant neoplasm of small intestine, unspecified
    C18.2Malignant neoplasm of ascending colon
    C18.7Malignant neoplasm of sigmoid colon
    C18.9Malignant neoplasm of colon, unspecified
    C19Malignant neoplasm of rectosigmoid junction
    C20Malignant neoplasm of rectum
    C21.8Malignant neoplasm of overlapping sites of rectum, anus and anal canal
    C26.0Malignant neoplasm of intestinal tract, part unspecified
    C50.912Malignant neoplasm of unspecified site of left female breast

    Showing 1–10 of 28

    Related Payer Policy Updates

    Specialty: Genetic & Molecular Testing1 / 3

    10 rows

    PolicyPayerEffective Date
    Oral Cancer Screening and TestingOscar Health2027-01-01
    RTM Testing for Alpha-1 Antitrypsin DeficiencyOscar Health2027-01-01
    Cytochrome P450 Genotype-Guided Treatment Strategy Corporate Medical Policybcbsvermont2027-01-01
    Carrier Testing Panels for Genetic Diseases (for Kentucky Only)UnitedHealthcare2026-10-01
    Genetic Testing for Neurological Disorders (for Kansas Only)UnitedHealthcare2026-10-01
    Genetic and Molecular TestingProvidence Health Plan2026-10-01
    Cell-Free Fetal DNA Testing (for Idaho Only)UnitedHealthcare2026-10-01
    Next Generation Sequencing for Minimal Residual Disease DetectionProvidence Health Plan2026-10-01
    Pharmacogenetic Panel Testing (for Kansas Only)UnitedHealthcare2026-10-01
    Non-Covered Genetic Panel TestsProvidence Health Plan2026-10-01

    Related Codes

    CPT-81105-HPA-1-PLATELET-ANTIGEN-1-GENOTYPING-ITGB3-CD61

    CPT 81105: HPA-1 (ITGB3/CD61) Genotyping, Technical Component

    CPT-81106-HPA-2-T145M-GENETIC-ALLELE-ANALYSIS

    CPT 81106: HPA-2 (T145M) Platelet Antigen Genotyping

    CPT-81107-HPA-3-GENETIC-ANALYSIS-TECHNICAL-COMPONENT

    CPT 81107: HPA‑3 (I843S) Platelet Antigen Genotyping

    CPT-81108-HPA-4-R143Q-GENOTYPING

    CPT 81108: HPA-4 (R143Q) Genotyping

    CPT-81109-HPA-5-K505E-GENETIC-ANALYSIS

    CPT 81109: HPA-5 (K505E) Genotyping Test

    CPT-81110-HPA-6-R489Q-GENOTYPING

    CPT 81110: HPA-6 (R489Q) Genotyping, Technical Component

    CPT-81111-HPA-9-V837M-ALLELE-ANALYSIS

    CPT 81111: HPA-9 (V837M) Genotyping, Technical Test

    CPT-81112-HPA-15-GENETIC-ANALYSIS-S682Y

    CPT 81112: HPA-15 (S682Y) Platelet Antigen Genotyping

    CPT-81120-IDH1-MOLECULAR-DIAGNOSTIC-TEST

    CPT 81120: IDH1 Mutation Detection, Technical Component

    CPT-81121-IDH2-MOLECULAR-DIAGNOSTIC-TEST

    CPT 81121: IDH2 Mutation Detection, Technical Component

    Showing 1–10 of 199

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    Frequently Asked Questions

    References

    1. 1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
    2. 2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
    3. 3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.
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