MDM2 once-protein is known to be involved in the inactivation of p53 and RE functions. We have investigated the expression of MDM2 protein in breast cancer by immunocytochemical analysis. Out of 103 primary tumors 39 (38%) showed positive nuclear staining of MDM2, although its gene amplification was infrequent. There was no correlation between MDM2 expression and various clinicopathological factors. However, MDM2 expression was significantly associated with expression of angiogenesis factors including vascular endothelial growth factor and platelet-derived endothelial cell growth factor. Anti-endothelial immunostaining demonstrated a correlation between MDM2 expression and the increment of intratumoral microvessel density. It is suggested that altered MDM2 protein expression might be involved in the promotion of angiogenesis in human breast cancer.