Persons who have been occupationally exposed to environmental mutagens have a substantially increased risk for somatic oncogene mutations. Structural mutation in viral kristen rat sarcoma oncogene homolog 2 (KRAS; v-Ki-ras 2) has been assessed as a mechanism of de-novo resistance to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibition in patients with non-small-cell lung cancer (NSCLC). The aim of the current study was to investigate the predictive significance of KRAS mutations in patient with NSCLC in relation to cigarette smoking and asbestos exposure. We have investigated 42 fresh tumoral tissue samples of cases that were histopathologically diagnosed as lung carcinomas. Patients were evaluated for clinical findings; tumoral tissue samples were examined histopathologically and genomic DNA from tumoral tissue samples were isolated. The KRAS point mutations were assessed by strip-Assay reverse hybridization method and compared with the healthy controls. A total of 24 patients (57%) demonstrated KRAS point mutations in their tumoral tissues, while 18 (43%) patients did not. Mutations were accumulated in current cases of NSCLC, which were active smokers and exposed to the asbestos. Current results showed that the combined effects of somatic mutations in KRAS may play an active role in development of primary lung carcinomas due to heavy smoke and asbestos exposure. Results also may have important implications for molecular diagnosis and targeted therapies in NSCLC.