Immunohistochemical detection of the p53 gene product by monoclonal antibodies has been shown to be associated with a poor clinical outcome in carcinomas of the breast and stomach. Because the prognostic relevance of p53 immunostaining in lung cancer is still under debate, we studied the expression pattern and clinical significance of such staining in 73 patients with operable non-small-cell lung cancer. p53 expression was detected on frozen sections with the use of monoclonal antibody p1801, which recognizes both the wild-type and mutant gene product (alkaline phosphatase-anti-alkaline phosphatase method). A tumor was considered p53 positive if more than 1% of the tumor cells were stained. The p53 expression pattern was compared with clinicopathologic parameters, and analysis of follow-up, based on the data of 65 patients, was done by a log rank test (median observation time, 780 days). Nuclear p53 staining was detected in 33 of 73 non-small-cell lung cancers (45.2%). Comparison with clinicopathologic parameters demonstrated that the p53 protein was detected more frequently in younger patients (younger than 50 years, p = 0.014), whereas no correlation was found with sex, tumor differentiation, tumor histologic type, or TNM stage. Surprisingly, follow-up analysis revealed that p53 staining was associated with an increased rate of disease-free survival, especially in patients with early stage tumor disease (p = 0.004) and in male patients (p = 0.023). Counter to previous studies in other solid tumors, immunocytochemical detection of p53 expression does not predict a poor clinical outcome in non-small-cell lung cancer. In early-stage lung cancer it might be associated with an improved disease-free survival, which suggests that the majority of the detected protein inherits the wild-type tumor suppressor function.