Background: Prostate-Specific Membrane Antigen (PSMA) has been known as a tumor associated neovasculature marker in some solid malignant tumors. Targeting of PSMA by cytotoxic-conjugated antibody can represent powerful tool for vascular targeted therapy. In thyroid, it appears that angiogenesis factors are involved in neoplastic growth and aggressiveness of tumors.This study was conducted to evaluate the expression of PSMA as an angiogenesis factor in neovasculature of thyroid follicular neoplasms by immunohistochemistry to determine its usefulness for distinguishing between adenoma and carcinoma.Methods: Paraffin Blocks of formalin fixed samples representing 48 cases of Follicular Thyroid Adenoma (FTA) and 15 cases of Follicular Thyroid Carcinoma (FTC) were evaluated.Results: Among 15 cases of FTC, 11 cases revealed both capsular and vascular invasion. In one case only capsular and in two cases only vascular invasions were observed. One case also revealed suspicious vascular invasion with further bone metastasis.The intensity of PSMA staining in vascular structures of carcinomas were significantly higher in comparison with thyroid follicular adenomas (p=0.028). However, we observed no significant difference in the extent of PSMA expression in adenoma and carcinoma groups (p=0.239).Thyroid follicular cells were negative for PSMA in adenoma, carcinoma and in non-neoplastic area. Conclusion:According to our findings, significant higher intensity of PSMA expression in FTC could be useful in differentiating between FTA and FTC. However, more importantly, expression in neovasculature of differentiated thyroid tumors can represent a potential utility for PSMA-targeted radionuclide therapy in advanced differentiated thyroid cancers.