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    v1.0.30
    OpenPayerBilling CodesGenetic Analysis ProceduresCPT cpt-81327-sept9-methylation-assay-colorectal-cancer-screening
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    CPT 81327: SEPT9 Methylation Test for Colorectal Cancer Detection

    CPT code 81327 describes a laboratory molecular diagnostic test that detects methylation of the SEPT9 (Septin9) gene promoter in circulating cell-free DNA from blood; this is a blood-based molecular pathology assay used as a tumor marker for colorectal cancer detection, typically performed as a clinical laboratory service with the technical processing done in a specialty molecular diagnostics laboratory or hospital lab and the specimen collected in an outpatient phlebotomy or clinic setting.

    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 58-year-old average-risk adult presents for colorectal cancer screening and declines colonoscopy. The clinician orders a blood-based SEPT9 methylation assay to detect circulating tumor DNA associated with colorectal neoplasia. A phlebotomy specimen is collected in the outpatient laboratory, labeled, and shipped to the reference molecular laboratory. The laboratory analyst performs the technical assay to detect methylated promoter regions of the SEPT9 gene in cell-free DNA extracted from plasma. Results are reported to the ordering physician, who incorporates the result into shared decision-making about further diagnostic evaluation (for example, colonoscopy if test is positive). Typical site of service is outpatient clinic, hospital outpatient laboratory, or independent reference laboratory performing molecular diagnostic testing. Common clinical workflow steps: order entry, patient consent and specimen collection, accessioning and processing, molecular assay performance, result verification by laboratory personnel, and final report transmission to the ordering clinician.

    Related CPT Codes

    CPT CodeDescriptionRelationship to This Procedure
    81327Methylation analysis of SEPT9 gene in circulating cell-free DNA for detection of colorectal carcinomaPrimary molecular assay code for detection of SEPT9 promoter methylation in plasma.
    36415Collection of venous blood by venipunctureCommonly performed immediately prior to sending specimen for 81327 testing.
    G0328Colorectal cancer screening; fecal DNA testing (deprecated in some payor policies)Alternative non-invasive screening test; may be considered in screening algorithms alongside or instead of blood-based testing.
    45380Colonoscopy, flexible; diagnostic, with or without collection of specimen(s)Diagnostic follow-up procedure commonly performed if 81327 is positive.
    88342Immunohistochemistry or special staining, per specimen; interpretive component (example for tissue follow-up)May be used in tissue-based confirmation after colonoscopic biopsy following a positive blood-based test.

    Related Modifiers

    7 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…
    91Modifier 91 — “Repeat Clinical Diagnostic Laboratory Test” — is appended when the exact same CPT laboratory test is performed more than once for the same patient on the same day because serial,…- Use modifier 91 when the exact same CPT laboratory test is performed more than once on the same patient on the same date because serial or repeated testing is medically necessary to monitor…
    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…
    53Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
    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…
    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…

    Related Provider Taxonomies

    8 rows

    Taxonomy Code
    208000000X
    207Q00000X
    207L00000X
    208800000X
    174M00000X
    372600000X
    385HR2065X
    111NX0800X

    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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