BACKGROUND: The aim of this study was to investigate the expression of bcl-2, p53 and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC), and to examine the relationship between those protein expressions and neovascularization. We also analyzed the prognostic impact of these biological parameters on the patients' overall survival rate. METHODS: The archival tumor tissues from 147 previously untreated patients with NSCLC were examined by immunohistochemistry for bcl-2, p53 and VEGF proteins. The vascularity was measured by the average microvascular density (MVD) of the CD34-positive vessels. Clinical information was obtained through the computerized retrospective database from the tumor registry. RESULTS: Immunoreactivity for bcl-2 was detected in 17% (25/147), p53 in 72% (106/147) and VEGF in 75% (110/147) of the tumors. An inverse association was found between bcl-2 expression and VEGF expression (p=0.012). There was a significant correlation between the bcl-2 expression and the MVD (p=0.009), and also between the p53 expression and the MVD (p=0.045). The mean survival time was associated with the patients' age (p=0.032), the T status (p=0.038), the tumor stage (p=0.009), and expressions of bcl-2 (p=0.016) and VEGF (p=0.039). On multivariate analysis, only the tumor stage and VEGF expression maintained their prognostic influence. CONCLUSIONS: Our data suggest that bcl-2 and p53 alterations are involved in the angiogenesis of NSCLC, and are either dependent on or independent of VEGF. It is further noteworthy that the tumor stage and VEGF expression may be useful in predicting patients' survival.