Neovascularization in the stroma of a tumor plays an important role in tumor growth and the establishment of metastases. The present study examined the immunohistochemical expression of vascular endothelial growth factor receptor 2 (VEGFR2) in 34 cases of oral squamous cell carcinoma (OSCC). Moreover, the relationships between parameters of tumor neovascularization (count of VEGFR2-positive [+] cells and total size of vessel lumen [TSVL]) and those of histology (differentiation type and mode of invasion) were analyzed statistically. Immunohistochemical expression of VEGFR2 was localized in stromal cells at the tumor invasive front. The VEGFR2+ cell count around poorly differentiated tumors was significantly higher than that around well differentiated tumors (P = 0.032, one-way ANOVA). The TSVL around the well differentiated type was found to be significantly larger than that around the poorly or moderately differentiated type (P < 0.001, respectively; one-way ANOVA). With regard to the mode of invasion, the TSVL was significantly larger for lower-grade (Grades 1+2) than for higher-grade (Grades 3+4) tumors (P < 0.001, unpaired t-test). On the basis of our results, we suggest that vascular development at the invasive front of OSCC is governed by the following factors: the tumor cells themselves may induce hemangiogenesis in the adjoining stromal tissue; hemangiogenic activity is higher when parenchymal intercellular adhesion is looser and when the parenchymal area exposed to the stroma is greater; and the rate of blood flow is higher when parenchymal intercellular adhesion is tighter and parenchymal nests are larger. (J Oral Sci 51, 551-557, 2009)