The aim of this study was to assess prospectively the occurrence of p53 and p16 mutations (considered separately and together) in NSCLC in terms of their clinical and prognostic relevance. Study group included 87 patients who underwent pulmonary resection for cure. p53 and p16 mutations were found in 22 (25%) and 14 (16%) cases, respectively. In eight patients (9%) both mutations were present, and the tendency for their common occurrence was significant (p = 0.02). There was no relation between mutation and clinical characteristics. Median survival in the entire group was 17 months and the 3-year survival probability--41%. There was no correlation between the occurrence of any mutation (considered separately or together) and survival. These results indicate that p53 and p16 gene mutations tend to occur together in NSCLC, however these alterations seem not to have noteworthy clinical and prognostic significance.