The expression of p27, which is known as a cyclin-dependent kinase inhibitor, on surgically resected specimens has considerable value for the prognosis of non-small cell lung cancer (NSCLC) patients. We immunohistochemically investigated the expression of the p27 protein in the biopsy specimens taken from 69 advanced NSCLC patients and assessed its clinical value. There was no significant correlation between p27 positivity and clinical parameters, including sex, age, histological type, clinical stage, smoking index and performance status. Furthermore, p27 positivity was not associated with response to chemotherapy. However, the Kaplan-Meier curve demonstrated that low p27 expression was significantly related to poor prognosis (P = 0.0019, by the log-rank test). Using multivariate analysis, p27, age and serum total protein level were found to be the independent prognostic parameters. The p27 positivity in the biopsy specimens of advanced NSCLC appears to be a useful prognostic marker.