CPT 81538: Serum Mass Spectrometry Prognostic Assay for Lung Cancer

CPT code 81538 describes a laboratory service in which a lab analyst performs technical mass spectrometry measurement of eight serum proteins (including amyloid A) and applies a predictive algorithm to report a patient’s likelihood of good versus poor overall survival from lung cancer; service type: laboratory test with algorithmic prognostic reporting; typical site of service: clinical laboratory or molecular diagnostics laboratory.

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CPT 81538: Serum Mass Spectrometry Prognostic Assay for Lung Cancer

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Get alerted when payer policies referencing 81538 are released or updated.

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Clinical & Coding Specifications

Clinical Context

A 64-year-old patient with a history of non–small cell lung cancer (NSCLC) presents during oncology follow-up to assist prognostic assessment after systemic therapy. The oncologist orders a serum-based proteomic prognostic test processed with mass spectrometry that measures eight proteins, including serum amyloid A, and runs a predictive algorithm to classify overall survival likelihood as "good" versus "poor." A phlebotomy draw is performed in the outpatient oncology clinic or a reference laboratory collection center. The blood specimen is shipped to a central laboratory with mass spectrometry capability. In the lab, a trained clinical laboratory scientist performs the technical steps: sample preparation, protein quantitation by mass spectrometry, quality control, and runs the algorithm that integrates the protein panel (and any allowable clinical data elements) to generate a prognostic report. The final report is routed to the ordering oncologist and uploaded to the electronic medical record to support care planning and patient counseling on prognosis and treatment strategy.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`36415`	Collection of venous blood by venipuncture	Venipuncture for serum collection prior to shipping to the testing laboratory
`81002`	Urinalysis, non-automated, by dipstick (reagent strip)	Ancillary lab tests sometimes performed in oncology workup though not directly required for this proteomic assay
`88360`	Immunohistochemistry or immunocytochemistry; initial single stain	Tumor tissue testing performed in parallel for diagnostic or prognostic information in lung cancer care
`0000U`	Proprietary proteomic prognostic algorithm (example of an FDA-cleared or proprietary test)	Representative of current molecular/proteomic tests billed with specific CPT-PLA or analyte-specific codes; used when alternate assay-specific code exists
`99213`	Office outpatient established patient visit	Clinic visit during which the test is ordered and results reviewed with the patient

Related Modifiers

5 rows

Modifier	Description	When to Use
26	Modifier 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…
90	Modifier ‑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…
91	Modifier 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…
52	Modifier ‑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…
53	Modifier 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…

Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
207RG0100X	Gastroenterology Physician	An internist who specializes in diagnosis and treatment of diseases of the digestive organs including the stomach, bowels, liver and gallbladder. This…
208100000X	Physical Medicine & Rehabilitation Physician	Physical medicine and rehabilitation, also referred to as rehabilitation medicine, is the medical specialty concerned with diagnosing, evaluating, and…
207L00000X	Anesthesiology Physician	An anesthesiologist is trained to provide pain relief and maintenance, or restoration, of a stable condition during and immediately following an opera…
207LP2900X	Pain Medicine (Anesthesiology) Physician	An anesthesiologist who provides a high level of care, either as a primary physician or consultant, for patients experiencing problems with acute, chr…
2081H0002X	Hospice and Palliative Medicine (Physical Medicine & Rehabilitation) Physician	A physical medicine and rehabilitation physician with special knowledge and skills to prevent and relieve the suffering experienced by patients with l…
207RC0001X	Clinical Cardiac Electrophysiology Physician	A field of special interest within the subspecialty of cardiovascular disease, specialty of Internal Medicine, which involves intricate technical proc…
225000000X	Orthotic Fitter	An individual trained in the management of fitting prefabricated orthoses.
283Q00000X	Psychiatric Hospital	An organization including a physical plant and personnel that provides multidisciplinary diagnostic and treatment mental health services to patients r…

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-81504-TUMOR-ORIGIN-RNA-EXPRESSION-CLASSIFIER

CPT 81504: Tumor RNA Expression Profile Comparison

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

Showing 1–10 of 41

Frequently Asked Questions

References

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.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.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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Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

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Clinical & Coding Specifications

Clinical Context

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`36415`	Collection of venous blood by venipuncture	Venipuncture for serum collection prior to shipping to the testing laboratory
`81002`	Urinalysis, non-automated, by dipstick (reagent strip)	Ancillary lab tests sometimes performed in oncology workup though not directly required for this proteomic assay
`88360`	Immunohistochemistry or immunocytochemistry; initial single stain	Tumor tissue testing performed in parallel for diagnostic or prognostic information in lung cancer care
`0000U`	Proprietary proteomic prognostic algorithm (example of an FDA-cleared or proprietary test)	Representative of current molecular/proteomic tests billed with specific CPT-PLA or analyte-specific codes; used when alternate assay-specific code exists
`99213`	Office outpatient established patient visit	Clinic visit during which the test is ordered and results reviewed with the patient

Related Modifiers

5 rows

Modifier	Description	When to Use
26	Modifier 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…
90	Modifier ‑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…
91	Modifier 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…
52	Modifier ‑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…
53	Modifier 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…

Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
207RG0100X	Gastroenterology Physician	An internist who specializes in diagnosis and treatment of diseases of the digestive organs including the stomach, bowels, liver and gallbladder. This…
208100000X	Physical Medicine & Rehabilitation Physician	Physical medicine and rehabilitation, also referred to as rehabilitation medicine, is the medical specialty concerned with diagnosing, evaluating, and…
207L00000X	Anesthesiology Physician	An anesthesiologist is trained to provide pain relief and maintenance, or restoration, of a stable condition during and immediately following an opera…
207LP2900X	Pain Medicine (Anesthesiology) Physician	An anesthesiologist who provides a high level of care, either as a primary physician or consultant, for patients experiencing problems with acute, chr…
2081H0002X	Hospice and Palliative Medicine (Physical Medicine & Rehabilitation) Physician	A physical medicine and rehabilitation physician with special knowledge and skills to prevent and relieve the suffering experienced by patients with l…
207RC0001X	Clinical Cardiac Electrophysiology Physician	A field of special interest within the subspecialty of cardiovascular disease, specialty of Internal Medicine, which involves intricate technical proc…
225000000X	Orthotic Fitter	An individual trained in the management of fitting prefabricated orthoses.
283Q00000X	Psychiatric Hospital	An organization including a physical plant and personnel that provides multidisciplinary diagnostic and treatment mental health services to patients r…

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-81504-TUMOR-ORIGIN-RNA-EXPRESSION-CLASSIFIER

CPT 81504: Tumor RNA Expression Profile Comparison

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

Showing 1–10 of 41

Frequently Asked Questions

References

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.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.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.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

OpenPayer

CPT 81538: Serum Mass Spectrometry Prognostic Assay for Lung Cancer

Sign up for cpt 81538 policy alerts

OpenPayer

CPT 81538: Serum Mass Spectrometry Prognostic Assay for Lung Cancer

Sign up for cpt 81538 policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Codes

References

CPT 81538: Serum Mass Spectrometry Prognostic Assay for Lung Cancer

Sign up for cpt 81538 policy alerts

CPT 81538: Serum Mass Spectrometry Prognostic Assay for Lung Cancer

Sign up for cpt 81538 policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Codes

What clinical service does CPT 81538 cover?

Which CPT modifiers are relevant when billing CPT 81538?

What related CPT codes should billing staff be aware of when submitting claims involving CPT 81538?

Which ICD-10 diagnoses are commonly paired with this prognostic proteomic assay?

Which payers are referenced as relevant for CPT 81538 and does the page provide coverage or payment amounts?

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related Codes

What clinical service does CPT 81538 cover?

Which CPT modifiers are relevant when billing CPT 81538?

What related CPT codes should billing staff be aware of when submitting claims involving CPT 81538?

Which ICD-10 diagnoses are commonly paired with this prognostic proteomic assay?

Which payers are referenced as relevant for CPT 81538 and does the page provide coverage or payment amounts?

References