We evaluated the presence of glomeruloid microvascular proliferations (GMPs) in 723 patients with melanomas, breast, endometrial, or prostate cancer. Presence of GMPs was associated with markers of aggressive tumor behavior and significantly reduced survival or increased clinical recurrences in all four of the cancer types in univariate analysis. GMPs were related to increased microvessel density in prostate cancer only. In the case of melanomas, breast, and prostate cancers (but not endometrial cancers), GMPs were a significant prognostic factor in the final multivariate models (P all <or= 0.02), and was a better predictor of outcome than was microvessel density. In conclusion, GMPs might indicate a more aggressive vascular phenotype associated with poor prognosis and could be a novel prognostic marker in human cancer.