Much attention has been focused on the role of angiogenesis in tumor growth and dissemination. Alternative forms of tumor-associated microcirculation exist and were first demonstrated by light microscopic histological techniques such as PAS-positive patterns in uveal melanomas. Since then several advances have been made in unraveling the true nature of these patterns, and have been documented in other tumors such as cutaneous melanomas and hepatic melanomatous metastases. These patterns, termed as "vasculogenic mimicry," are distinctly different from endothelial cell-lined blood vessels and may contribute significantly as an alternative supply to the tumors' overall microcirculation. The molecular events that regulate the formation of these patterns in tumors, their constituent nature and the ability to demonstrate these patterns by non-invasive techniques provide further opportunities for enhanced detection, early prognostication and the development of targeted therapies.