Vascular endothelial growth factor (VEGF) functions as a regulator of neovascularization in malignant cells. VEGF as a mitogen is thought to alter renal cell carcinoma formation and tumor progression. We investigated the expression of the VEGF gene in order to evaluate its clinical significance in renal cell carcinoma. Tissue samples from 198 patients with renal cell carcinoma were examined with an immunohistochemical stain for the expression of the VEGF gene. The expression rate was compared to 34 normal renal cortical samples obtained from renal surgery from noncancer patients. There were significant differences between normal renal cortex (0%) and cancer tissue (54.5%) in positive staining of VEGF protein (P<0.001). With the progression of tumor grade, the positive rate of VEGF gene expression significantly increased. The expression rate of the VEGF gene in the advanced group, such as with lymph node involvement or vein invasion, was greater than that in the locally confined group (P<0.001). The results revealed that expression of the VEGF gene is proportional to the formation and progression of renal cell carcinoma, which may allow VEGF to be used as a prognostic marker for renal cell carcinoma. J. Clin. Lab. Anal. 17:85–89, 2003. © 2003 Wiley-Liss, Inc.