PURPOSE: Galectin-3 and HBME-1 have been recognized as useful markers for the diagnosis of the thyroid lesions. In this study, we investigated whether they have a diagnostic value for nodular lesions of the thyroid. METHODS: We investigated the galectin-3 and HBME-1 expressions in 14 nodular hyperplasias, 30 papillary carcinomas, 17 follicular adenomas and 8 follicular carcinomas with using immunochemistry. RESULTS: Galectin-3 was positive in 96.7% of the papillary carcinomas and this incidence was significantly higher (P=0.0001) than that of nodular hyperplasia, 7.1%. However, the galectin-3 expressions of follicular adenoma and follicular carcinoma were not significantly different. HBME-1 was positive in 50.0% of the follicular carcinomas and this incidence was significantly higher (P=0.0001) than that of follicular adenoma. CONCLUSION: Galectin-3 and HBME-1 may be useful markers to diagnose papillary carcinoma. Although HBME-1 contributes to differential diagnosis of follicular adenoma and follicular carcinoma, further study is required.