The aim of our study was to gain further insight into the role of angiogenesis in Ewing's sarcoma. To this end, expression of Vascular Endothelial Growth Factor-A (VEGF-A), its receptors VEGFR-1 and -2 and microvessel density (MVD) were evaluated by quantitative immunohistochemistry in pretherapeutic biopsies of 40 patients with Ewing's sarcoma treated within standardised neoadjuvant protocols. Median expression levels were 1.5 arbitrary units (AU) for VEGF-A, 8.2 AU for VEGFR-2 and median MVD was 96/0.26 mm(2). VEGFR-1 was expressed in 12.5% of the samples, only. Ten-year relapse free and overall survival rates were significantly higher for patients with high VEGF-A expression (60% versus 29%, p=0.0216 and 65% versus 25%, p=0.013, respectively). Multivariate Cox regression analysis revealed that VEGF-A expression was an independent prognostic factor for survival. In conclusion, these data suggest that the angiogenic mediator VEGF plays an important prognostic role in Ewing's sarcoma.