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    v1.0.30
    OpenPayerBilling CodesMultianalyte Assays with Algorithmic AnalysesCPT cpt-81504-tumor-origin-rna-expression-classifier
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    CPT 81504: Tumor RNA Expression Profile Comparison

    CPT code 81504 reports a molecular diagnostic assay that compares RNA expression patterns from a tumor of unknown primary to a reference tumor database to help identify tissue or tumor type; this service is a molecular pathology / genomic profiling test typically performed on tumor tissue specimens in a specialty laboratory or clinical molecular diagnostics laboratory and is billed as a discrete diagnostic sequencing/analysis service using the CPT coding system.

    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 presents with a metastatic tumor identified on imaging but without a definitive primary site after standard pathology and immunohistochemistry. The oncology team orders an RNA expression profiling assay to compare the tumor's gene expression signature against a reference tumor database to suggest the most likely tissue or tumor type of origin. A formalin-fixed paraffin-embedded (FFPE) tumor specimen or extracted RNA is sent from the pathology laboratory to a reference molecular diagnostics laboratory. The laboratory performs extraction, quality control, RNA sequencing or targeted expression profiling, bioinformatic analysis to generate a similarity score, and a report that includes the top probable tumor types and confidence metrics. The result informs tumor-directed systemic therapy selection, targeted therapy considerations, and decisions about additional diagnostic workup. Typical sites of service include outpatient pathology laboratories, independent molecular diagnostic reference labs, hospital-based molecular labs, and cancer center specimen collection areas. Billing occurs under the molecular pathology/proprietary algorithm code 81504 for the tumor origin RNA expression comparison service.

    Related CPT Codes

    CPT CodeDescriptionRelationship to This Procedure
    88342Immunohistochemistry or special staining (per specimen)May be performed prior to or in parallel with RNA profiling to characterize tumor markers and guide selection of molecular tests.
    81275BRAF (V600) gene analysis (e.g., sequencing)Targeted mutation testing often follows expression profiling when a likely tumor origin suggests actionable mutations to test.
    81445Oncology (multi-gene panel) genomic sequence analysis panelBroader genomic panels may be ordered in addition to expression-based origin testing to identify actionable alterations.
    0000FPerformance and reporting codes (not an actual CPT)Data not available in the input.

    Related Modifiers

    6 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…
    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…
    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…
    99Modifier 99 is a placeholder modifier used when more modifiers apply to a single procedure than the claim form or electronic field allows. The AMA classifies it under Provider Services and Ambulatory…- Use CPT modifier -99 when more modifiers apply to a single procedure line than the claim form or payer field allows (CMS/Noridian: when more than four modifiers are needed); append modifier 99 on…

    Related Provider Taxonomies

    8 rows

    Taxonomy Code
    208000000X
    2086S0102X
    207Q00000X
    163WP0808X
    225XR0403X
    133NN1002X
    332H00000X
    207SC0300X

    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-81490-RA-DISEASE-ACTIVITY-SCORE-SERUM-BIOMARKER-PANEL

    CPT 81490: Serum Biomarker Panel and RA Disease Activity Score

    CPT-81493-CORONARY-ARTERY-DISEASE-23-GENE-RT-PCR-RISK-SCORE

    CPT 81493: 23-Gene RT-PCR Molecular Test With CAD Risk Score

    CPT-81500-CA125-HE4-ALGORITHMIC-RISK-SCORE

    CPT 81500: Algorithmic Risk Score Using CA-125 and HE4

    CPT-81503-ALGORITHMIC-LAB-RISK-SCORE-CA125-APOLIPOPROTEIN-A1

    CPT 81503: Algorithmic Risk Score from Multiple Lab Markers

    CPT-81506-DIABETES-BIOMARKER-PANEL-WITH-RISK-SCORE

    CPT 81506: Diabetes Risk Score from Biochemical Assays

    CPT-81507-NIPS-CELL-FREE-DNA-TRISOMY-RISK-ANALYSIS

    CPT 81507: Noninvasive Prenatal Testing for Trisomies 13, 18, 21

    CPT-81508-PAPP-A-HCG-ALGORITHMIC-RISK-ASSAY

    CPT 81508: First-Trimester PAPP-A and hCG Risk Score

    CPT-81509-LAB-ALGORITHMIC-RISK-ASSESSMENT-PAPP-A-HCG-DIA

    CPT 81509: Prenatal Biochemical Risk Score from PAPP–A, hCG, DIA

    CPT-81510-PRENATAL-TRIPLE-MARKER-ALGORITHMIC-RISK-ASSESSMENT

    CPT 81510: Prenatal Serum Screening with Algorithmic Risk Score

    CPT-81511-MULTIANALYTE-SERUM-SCREENING-ALGORITHMIC-RISK-SCORE

    CPT 81511: Maternal Serum Quadruple Marker Risk Score

    Showing 1–10 of 41

    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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