Purpose: Neovascularization has profound effects on tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a mitogen that acts exclusively on endothelial cells. The roles of miscrovascularity density (MVD) and VEGF expression in the progression of oral squamous cell carcinoma (OSCC) have been controversial. The purpose of the present study was to measure the MVD and VEGF expression in a cohort of patients with betel-associated OSCC and to evaluate for possible clinicopathologic correlations.Patients and Methods: The paraffin sections from 49 subjects with OSCC were subjected to immunohistochemical studies to measure the highest MVD (h-MVD) and cytoplasmic immunoreactivity of VEGF. The findings in the tissue samples were analyzed with regard to the patients' risk factors and clinical course.Results: The OSCC samples had an average h-MVD score of 27.7/mm 2 . VEGF immunoreactivity was positive in 75.5% of samples. Both h-MVD and VEGF immunoreactivity were statistically associated with lymph node metastasis (P = .012 and .037, respectively). A marginally significant association was also noted between the h-MVD and patient survival (P = .056). The age and oral habits of patients, as well as the tumor site and size, did not appear to be correlated with h-MVD or VEGF immunoreactivity.Conclusion: The data suggest that both h-MVD and VEGF immunoreactivity may be useful predictors for the progression of a subset of OSCC associated mostly with betel use. Antiangiogenesis therapy might have a role in reducing regional metastasis.