Although vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 are involved in angiogenesis of various cancers, clinical utility of preoperative serum concentration of these molecules in non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we determined the concentration of VEGF, MMP-9 and various other tumor markers in serum prior to surgery and evaluated the results compared with intratumoral vasculature to isolate a valuable marker in determining the prediction of angiogenesis in NSCLC. Among these molecules and serum tumor markers, circulating serum VEGF was identified to markedly correlate with microvessel density (MVD) of the resected tumor specimens. Moreover, overall survival of patients with low VEGF levels (< or =326 ng/ml) was significantly greater than that of patients with high VEGF levels (>326 ng/ml), while patients with low MMP-9 levels (< or =189 ng/ml) and those with high MMP-9 levels (>189 ng/ml) revealed similar overall survival. Conclusively, preoperative concentration of serum VEGF may be the most valuable marker in the prediction of intratumoral angiogenesis and prognosis of patients with NSCLC.