Grafting of mammalian cells and tissues to the chick embryo chorioallantoic membrane (CAM) is a well-established experimental system to evaluate many different parameters of tumor growth, and B16-F10 murine melanoma cell line has been successfully used to study metastatic process in the CAM assay. The aim of this study was to demonstrate the capability of B16-F10 melanoma cells to contribute to the new formation of host blood vessels through a vasculogenic mimicry mode. Results have shown that B16-F10 melanoma cells are able to form in 4 days macroscopic tumor masses and induce a strong angiogenic response comparable to that of a well-known angiogenic cytokine, namely fibroblast growth factor-2. Moreover, tumor cells are able to cross the chorionic epithelium, and to move beneath in the mesenchyme to form tumor masses immunoreactive to specific antibodies anti-S100 and anti-MART-1/Melan-A. Finally, we have shown that CAMs new-formed blood vessels are lined by both pigmented melanoma cells and cells immunoreactive to MART-1/Melan-A and PAS, suggesting the occurrence of a vasculogenic mimicry process.