Angiogenesis is important for the growth and metastasis of solid tumors. Some growth factors, inflammatory cytokines, and angiogenin are known to promote tumor angiogenesis. Among them, Vascular endothelial growth factor (VEGF) is the most intriguing factor in regard to tumor angiogenesis. Inhibition of VEGF activity by neutralizing antibodies or by the introduction of dominant negative VEGF receptors into endothelial cells of tumor-associated blood vessels resulted in the inhibition of tumor growth and in tumor regression, indicating that VEGF is a major initiator of tumor angiogenesis. VEGF promotes angiogenesis through their receptors, Flt-1 and Flk-1/KDR. on vascular endothelial cells. These two receptors were usually believed to be expressed specifically on vascular endothelial cell. Several reports have now shown that VEGF is not only significantly associated with microvessel density but also has prognostic value in both node-negative and node-positive oral squamous cell carcinoma. For many years several histologic features of the neoplasms are being considered when assessing the influence of malignancy grading on recurrence and prognosis. Among the characteristics investigated, degree of keratinization, nuclear pleomorphism, mode of invasion, microscopic depth of invasion, intravascular invasion, lymphocyte infiltration, and number of mitoses have been considered as important prognostic factors. So, this study was conducted to evaluate the correlation of vascular endothelial growth factor expression with malignancy in paraffin-embedded biopsy specimens from 11 patients with tongue cancers. Our results showed that high immunoreactivity specimens of VEGF expression were significantly lower keratinization degree and more pronounced nuclear pleomorphism than in low immunoreactivity specimens. Thus, VEGF expression could be used as a prognostic marker in tongue cancer.