Clinical importance of tumor angiogenesis, especially its significance as a prognostic indicator, was examined in 125 primary breast-cancer patients. The grade of neovascularization was assessed by the vessel density which was obtained by immunocytochemical staining for factor VIII antigen. Post-operative survey demonstrated that the vessel density is a statistically significant predictor of relapse-free survival (median follow-up period: 62 months). Patients with over 100 counts of factor-VIII antigen-positive cells per 200 x field in the most active areas of neovascularization showed significantly poorer prognosis than those with less than 100 counts. The prognostic value of the vessel density was also confirmed by another evaluation method using immunocytochemical staining to CD-31 which is a platelet/endothelial cell adhesion molecule. A significant difference in relapse-free survival rate was shown between patients having higher counts of CD-31 positive cells and those having lower counts. Breakdown analysis stratified by nodal status showed that the vessel density was a significant prognostic indicator in node-negative and node-positive patients. Multivariate analysis indicated that the vessel density is an independent prognostic indicator in primary breast-cancer patients.