INTRODUCTION: Angiogenesis is decisive in tumour progression and metastasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and increased VEGF levels in patients with carcinomas may facilitate growth of both primary and secondary tumours. METHODS: Soluble (s) VEGF levels were determined in serum from 91 volunteer healthy blood donors and from 614 patients scheduled to undergo resection for primary colorectal cancer. None of the patients received pre- and/or post-operative chemo- and/or radiotherapy. The results of sVEGF were analysed with respect to Dukes>> stage, gender, age and topographical tumour localization. RESULTS: Patients with colorectal cancer had significantly (P<0.0001) higher levels of sVEGF, compared to healthy blood donors. Patients with Dukes>> stage D disease had significantly (P=0.01) higher values than patients with Dukes>> stage A, B and C disease, who had comparable values. Patients with the primary tumour localized in the colon had significantly (P<0.0001) higher levels of sVEGF than patients with the primary tumour localized in the rectum. By classifying the patients into two groups, based on the upper limit of the 95(th)percentile of sVEGF of healthy individuals (sVEGF=465 pg/ml), we found a significantly (P<0.0001) reduced overall survival in patients with sVEGF >465 pg/ml compared to patients with sVEGF values below this level. Moreover, in the subgroup of patients with the carcinoma localized in the colon and sVEGF levels above 465 pg/ml, we found a significantly (P<0.0001) reduced overall survival compared to colon cancer patients with lower sVEGF values. In conclusion, data from the present study suggest a biological significance of VEGF in patients with colorectal cancer, and indicate that a high pre-operative sVEGF value is associated with poor outcome, but further research is needed to validate sVEGF as a cancer marker.