We evaluated some proposed molecular thyroid tumor markers: thyroid peroxidase (TPO), galectin-3, cytokeratin-19, and HBME-1, individually and in combination, by immunohistochemistry in a total of 242 archival thyroid tissue sections. The expression of each individual marker was most helpful for the diagnosis of papillary carcinoma and its follicular variant. However, none of them was sensitive and specific enough to discriminate between Hürthle adenoma and carcinoma. Galectin-3 and HBME-1 could be used as single discriminators between follicular thyroid adenoma and carcinoma, but HBME-1 is the better choice. As a single test, all analyzed tumor markers had sufficient power to predict differentiated thyroid cancer, with sensitivities ranging from 66.5% to 82.2%. The sensitivity was improved by using combinations of some proposed markers. Only two antigens, HBME-1 and TPO, had distinct predictive values for different diagnostic alternatives i.e. a sequential combination improved diagnostic accuracy between follicular thyroid adenoma and the follicular variant of papillary thyroid carcinoma to 92.6% and consequently, between overall benign and malignant thyroid tumors to 89.1%. HBME-1 is the most accurate ancillary stain in discriminating well-differentiated thyroid carcinomas from benign tumors, although the addition of TPO did improve accuracy and served as a useful confirmatory marker.

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