We examined 77 non-small cell lung cancer (NSCLC) cell lines for mutations of 3 ras genes and p53 gene, and ras mutations were detected by designed RFLP assay generated by mismatched primers during the PCR step and p53 gene mutations were detected using SSCP analysis. The incidence of ras mutations were 27/77 (35%) while that of p53 gene mutations were 57/77 (74%). The incidence of ras mutations in cell lines with p53 mutations were not different from that without p53 mutations, suggesting that they occurred independently. Neither ras nor p53 mutations correlated with histologic subtype, disease extent, in vitro culture time nor prior therapy status. The patients whose cell lines had any ras mutations survived for shorter period of time not only among the patients who were treated with curative intent but among those treated with palliative treatment. The Cox proportional hazards model predicted the higher risk for patients with ras mutations but not those with p53 mutations. We conclude that ras and p53 mutations are frequent, apparently independent genetic alterations which play different roles in NSCLC and that this information should be utilized in surgical oncology in the near future.