Angiogenesis is involved in tumor progression of oral squamous cell carcinoma (OSCC). In this study, we have investigated by immunohistochemistry vascular endothelial growth factor (VEGF) expression in tumor cells and we have correlated VEGF expression to microvessel area, evaluated by using CD105 as a marker of endothelial cells, in bioptic specimens of 54 human OSCC. Results demonstrated that VEGF is highly expressed in OSCC tumor specimens when compared to pre-neoplastic and normal tissues, without differences between the edge and inside the tumor. Moreover, VEGF expression is reduced in poor differentiated OSCC tumors when compared to moderate and good differentiated forms, and tumor microvessel area is higher in tumors when compared to pre-neoplastic lesions and normal tissues. Finally, VEGF and CD105 may be considered as reliable markers of tumor angiogenesis and progression in OSCC, even if we did not demonstrate any correlation between VEGF expression, tumor microvascular area, clinical stage, and lymph node status.