Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) play a key role in vasculogenesis and angiogenic sprouting, which are crucial for tumour development and metastasis. In order to determine their possible role in the acquisition of metastatic potential throughout melanocytic tumour progression, VEGF and VEGFR-2 immunohistochemical expression were evaluated in 36 human melanocytic tumours of the skin (24 malignant melanomas and 12 common naevi). Different VEGFR-2 immunostaining patterns were detected in the vast majority of melanomas (21/24; 88%). A nuclear membrane-like pattern was mainly associated with in situ and microinvasive melanomas, whereas a combined cytoplasmic membrane and nuclear membrane-like pattern was seen in invasive melanomas. A nuclear membrane-like pattern was also observed in 83% (10/12) of common naevi. Cytoplasmic immunostaining for VEGF was observed in 72% (8/11) of in situ/microinvasive melanomas, 84% (11/13) of invasive melanomas and 91% (11/12) of naevi. CD31 was also investigated as an immunohistochemical marker for microvessel density (MVD) evaluation. No associations were found between MVD and VEGF/VEGFR-2 expression. Taken together, these data indicate that VEGF production is a common event in benign melanocytic tumours, whereas VEGFR-2 expression, co-localized in the cytoplasmic and nuclear membrane, is associated with progression towards invasive melanoma. The role exerted by VEGF/VEGFR-2, however, seems to be independent of the development of a tumour-related capillary network.