Background: The accurate diagnosis of a thyroid nodule is important in deciding a patient's treatment plan and for predicting the prognosis. The histopathological diagnosis of resected specimens are largely positively accomplished, but the consistency of the diagnosis is low when the specimen shows a small carcinomatous cytological feature or the nodule does not express papillary proliferation. Therefore, the need for supplementary diagnostic measures is increased. Herein, the expressions of galectin-3 and thyroid peroxidase (TPO) of resected specimens were investigated using immunohistochemical staining, and their potential for contributing to an accurate diagnosis studied. Methods: The specimens included 195 resected thyroid nodules obtained from 179 patients having undergone thyroid surgery. Immunohistochemical staining for two useful antibodies, galectin-3 and TPO, were performed, and the expressions of these two antibodies investigated with regard to the histological diagnosis. Results: The sensitivity, specificity, and positive and negative predictive values of galectin-3 and TPO for detecting papillary carcinomas were all 100%, but these values were low for other forms of carcinoma. Conclusion: Our data showed the diagnosis of thyroid nodules, using immunohistochemical staining for galectin-3 and TPO, was very useful for detecting thyroid papillary carcinoma, but insufficiently sensitive for follicular carcinoma. Immunohistochemical staining for TPO is also useful for distinguishing cases when a false positive result for galectin-3 is obtained. (J Kor Endocrine Soc 22:105~111, 2007) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ