We aimed to determine the immunoreactivity for B-type Raf kinase (BRAF), , Hector Battifora mesothelial-1 (HBME-1), and Galectin-3 (GAL-3) antibodies in single and combination forms to define their potential role on diagnosis in encapsulated follicular thyroid tumors creating diagnostic difficulties. One hundred thirty five thyroid tumors diagnosed with follicular adenoma (FA, n=50), encapsulated minimally invasive follicular carcinoma (MIFC, n=40), and encapsulated follicular variant of papillary carcinoma (FVPC, n=45) were evaluated for immunohistochemically. For a single antibody, HBME-1 was the most sensitive antibody for the diagnosis of FVPC vs FA (93,33%), whereas CK-19 had the lowest sensitivity among the 4 markers. HBME-1 + GAL-3 combination has the most sensitivity value (67,5%) for diagnosing MIFC vs FA. The combination of CK19+HBME1+GAL3 and CK19+HBME1+BRAF have the highest sensitivity values (62,5%) for diagnosing FK vs FA. The coexpression of the four antibodies showed average sensitivity and high specificity results as 60-65% in sensitivity and 80% in spesifity for MIFC vs FA; FVPC vs FA and FVPC vs MIFC. For optimum sensitivity and specificity, the combination of the four markers was suggested for the diagnosis of MIFC vs FA. In conclusion, immunohistochemical evaluation of BRAF, CK-19, HBME-1 and GAL-3 in tyhroid tumors would aid the differentiation of malignant follicular lesions from benign follicular lesion. Combination of different forms of antibodies in accordance with the lesion type to be distinguished may increase the sensitivity of diagnosis, which needs to be confirmed with further studies.