The present study was designed to detect changes in p53 and MDM2 protein expression patterns in plasma from lung cancer patients. The largest p53 protein expression was observed in adenocarcinoma patients; however, mutant p53 was not increased in any cancer sample. A significant increase in the 57-kDa MDM2 isoform was observed in adenocarcinoma patients with low protein expression of the 90-kDa isoform. Our findings suggest that p53 accumulation could be due to a decrease in full-length MDM2 isoform together with an increase of the 57-kDa MDM2 isoform that was unable to stimulate p53 degradation.