Objective：To investigate the usefulness of immunohistochemical expression and immunolocalization of a panel of papillary thyroid carcinoma markers including HBME-1，CK19 and Galectin-3. Methods：By immunochemical EnVision method, the expression of HBME-1，CK19 and Galectin-3 were detected in 55 cases of papillary thyroid carcinomas，24 follicular adenomas, 20 multinodular goiters and 10 Hashimoto’s thyroiditis. Results：The rates of immuno-positive staining of HBME-1，CK19 and Galectin-3 in papillary thyroid carcinoma were 96.4%，98.2% and 94.5%, respectively, which were significantly higher than that of benign lesions（20.4%, 20.4% and 22.2%, respectively）. No significant relationship was found among the expressions of HBME-1, CK19 and Galectin-3. The sensibility, specificity，positive predictive value, negative predictive value and accuracy rate of using HBME-1 combined with CK19, Galectin-3 in differentiation benign from papillary thyroid carcinoma were 100%, 96.9%, 98.8%, 98%, 100% respectively. Conclusion：An immunohistochemical panel consisting of HBME-1, CK19 and Galectin-3 can make a correct differential diagnosis between papillary thyroid carcinoma and its benign mimics.