Alteration of the p53 tumor suppressor gene is one of the most frequently seen molecular lesions in human lung cancer. It is of importance to integrate translational science into clinical practice. In our laboratory, we are in search for clinical utility of p53 gene alterations in management of patients with lung cancer. Here, we would like to discuss p53 alterations as a prognostic factor for lung cancer patients or as a predictor of chemosensitivity.