OBJECTIVES: Depending on the penetration of screening recommendations, it is possible that the incidence of detected pulmonary nodules (PNs) could increase exponentially in coming years. Currently PN evaluation routinely requires costly procedures including imaging, biopsy and surgery. A molecular blood based test that measures plasma proteins using selected reaction monitoring mass spectroscopy allows for an objective and quantitative assessment of PN benignity. This budget impact analysis was performed to quantify the molecular test impact on a US commercial health plan’s direct medical costs. METHODS: The budget impact model was developed from a commercial health plan perspective, with direct medical costs estimated from the MarketScan® reimbursement benchmark data. Total PN diagnostic evaluation costs were estimated for a 2-year time horizon and were calculated for the current standard of care and care with the introduction of the molecular test. Diagnostic procedure resource utilization was obtained from a retrospective chart review analysis of a geographically representative sample of indeterminate PNs (8-20mm) managed by outpatient pulmonologists. RESULTS: Currently, 52% of PNs are evaluated with an invasive procedure (biopsy/surgery) and 48% with surveillance alone, with significant cost differences observed between these two groups. The base case analysis using a health plan of one million members and a rate of 0.25% PNs within the health plan, estimated a 27% reduction in avoidable invasive procedures with the introduction of the molecular test. This amounted to a total potential cost savings of 20% from procedure and complication avoidance. CONCLUSIONS: Adoption of this molecular test may help reduce the number of unnecessary invasive procedures being performed for individuals presenting with indeterminate pulmonary nodules. The reduced resource utilization can result in cost savings for the health plan.