BACKGROUND: The usefulness of serum proteomic test (VeriStrat) in African-Americans with non-small cell lung cancer (NSCLC) as well as the relationship between comorbidity and test performance have not been studied. MATERIALS AND METHODS: We reviewed records of patients with NSCLC in our practice for whom VeriStrat was performed to assist with the selection of therapy. We correlated survival with VeriStrat test classification, race, and comorbidity index using SAS software 9.4. RESULTS: We identified 49 qualified patients; 33 with VeriStrat Good (VSG), 16 with VeriStrat Poor (VSP). When stratified by VSG vs. VSP, overall survival (OS) did not differ between African-Americans and Whites [hazard ratio (HR)test (VSG/VSP)=0.78, 95% confidence interval (CI)=0.38-1.61; p=0.51]. OS adjusted for mean Charlson Comorbidity Index (CCI) was not different between erlotinib- and chemotherapy-treated groups in patients with non-squamous NSCLC (adjusted HR=0.91, 95% CI= 0.37-2.23; p=0.84), but was inferior in patients with squamous NSCLC treated with erlotinib (adjusted HR=10.6, 95% CI=1.28-87.8; p=0.029). Cox proportional hazard model for OS effect of VeriStrat test was estimated after adjusting for CCI. In both the VSG and VSP groups, a higher CCI value was associated with lower survival, and at any CCI value, the VSG group had better survival than the VSP group. CONCLUSION: Our study corroborates that race does not influence prognostic and predictive values of VeriStrat; however, comorbidities have a significant impact on survival in each proteomic stratum.