OBJECTIVES: Life Technologies has developed a 14-gene molecular assay (Pervenio^TM Lung RS) that provides mortality risk stratification in resected early-stage non-squamous NSCLC. The test classifies patients as low, intermediate, or high-risk (for death), informing decisions about adjuvant chemotherapy use. Accordingly, high-risk patients may benefit from chemotherapy, and low-risk patients can avoid chemotherapy-associated morbidity and costs.  Our objective was to estimate the budget impact of covering the assay in hypothetical commercial and Medicare health plans. METHODS: We developed a Markov model to estimate costs before and after coverage of the 14-gene RS in commercial (age <65) and Medicare (age 65+) health plans with 1 million enrollees. Health plan age distributions and disease incidence were derived from the U.S. census and SEER, respectively. Risk-group classification was based on 14-gene RS clinical studies, and chemotherapy uptake was based on a study of pre/post testing recommendations from 58 surgeons/oncologists. Included costs were those of the assay, chemotherapy with NCCN-recommended regimens, monitoring, post-recurrence care, and adverse events.  We calculated the total and per-member per-month (PMPM) 1-year budget impact of adding coverage for the 14-gene RS, and evaluated uncertainty using one-way sensitivity analyses.   RESULTS: The 1-year budget impact of covering the 14-gene RS assay in commercial and Medicare health plans with 1 million members is expected to be $24,200 (PMPM=$0.002) and $178,800 (PMPM=$0.015), respectively. The most influential parameters were the proportion of high-risk patients receiving chemotherapy, the chemotherapy recurrence hazard ratio, and the proportion of patients receiving initial surgical treatment.  CONCLUSIONS: Our analysis suggests that covering the 14-gene RS assay is expected to increase chemotherapy use, decrease recurrences, and result in a small net increase in PMPM cost in commercial and Medicare health plans. These outcomes indicate that the assay has the potential to provide positive health outcomes for health plan members at a reasonable cost.