Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies. Several recent reports have documented overexpression of VEGF in papillary thyroid cancer. We studied the relationship between increased expression of VEGF and an increased risk of recurrence. The aims of this study were to determine whether immunohistochemical expression of VEGF is related to local and distant recurrence of papillary thyroid cancer and to evaluate the relationship between hypervascularization and VEGF expression in papillary thyroid carcinoma. VEGF expression was examined immunohistochemically in 45 papillary carcinomas. Ten patients with normal thyroid glands who underwent surgery between 1991 and 1992 were used as controls. All patients were followed for 12 years. Fifteen of the patients had local and distant recurrences. VEGF immunostaining was evaluated semiquantitatively by a pathologist. The difference between the recurrent (n = 15) and nonrecurrent (n = 30) carcinomas was statistically significant (P = 0.001). VEGF expression was also stronger in papillary thyroid carcinomas than in normal thyroid tissues (P = 0.001). There was a statistically significant correlation among the tumor size, regional recurrence, distant metastasis, and the VEGF expression. These data indicate that VEGF staining is strongly associated with an increased frequency of recurrence in papillary thyroid cancer and that the immunohistochemical profile of the expression may be used as a marker for predicting which tumors have metastatic potential.