BACKGROUND: Angiogenesis has been demonstrated to associate with various measures of tumor aggressiveness in many human malignancies. However, studies of tumor angiogenesis in oral squamous cell carcinoma (SCC) are still unclear. Recent studies indicate non-angiogenesis mechanism (tumor-lined vessel) may exist in certain tumors. Therefore, we investigate microvessel density (MVD) and tumor-lined vessel in oral SCC. METHODS: Peritumoral and intratumoral MVD were measured by immunohistochemical staining. Tumor-lined vessels were identified by double staining. Statistical analysis of peritumoral and intratumoral MVD and presence of tumor-lined vessels with clinicopathologic parameters was performed. RESULTS: The results showed peritumoral MVD increased with disease progression and further increases of intratumoral MVD was detected by CD31 and CD34. Non-angiogenesis, tumor-lined vessel, presented in oral SCC and correlated significantly with tumor size, stage, and histologic differentiation. CONCLUSION: Our results suggest at the initiation of oral SCC, increasing vascularity is observed at the periphery of the tumor. As the tumor continues to grow, further increases of intratumoral vascularity and the presence of tumor-lined vessels are associated with cancer progression.