The purpose of our study was to examine the prognostic significance of different biomarkers [DNA content, proliferating cell nuclear antigen labeling index (PCNA-LI), p53 mutation and apoptosis], in 152 surgically resected non-small cell lung cancer (NSCLC). The ploidy was carried out by densitometry; PCNA-LI, p53 and apoptosis were determined with immunohistochemistry. The results were correlated to histology, stage and patient survival. A considerable variability of the PCNA indices, ranging from 0 to 33.5% with a mean value of 7.0%, was found. DNA evaluation showed a prevalence of aneuploid tumors (62%) with a DNA index >1. Overexpression of p53 protein and apoptotic positivity were observed in low percentages of cases (16% and 32% respectively). Only stage and PCNA-LI were found to be significant prognostic factors on multivariate analysis. PCNA was superior to stage in predicting shortened survival of patients with NSCLC. PCNA immunostaining can be applied on a routine basis in formalin-fixed, paraffin-embedded samples of NSCLC to predict patient prognosis and thus to identify patients in need of additional postoperative therapies.