Purpose: This study aimed to evaluate the expression pattern of galectin-3 and β-catenin and assess the nuclear morphometric features of different thyroid lesions in order to investigate their diagnostic significance. Materials and methods: Sixty specimens of benign and malignant thyroid lesions, in addition to 10 cases of normal thyroid tissue used as control, were immunohistochemically stained with antibodies against galectin-3 and β-catenin. Hematoxylin and eosin-stained slides were examined using image analyzer Proplus V software. Morphological parameters measured included mean nuclear diameter, mean nuclear perimeter, and mean nuclear area. Results: Cytoplasmic immunoreactivity for galectin-3 was strongest in papillary thyroid carcinomas (88.9%), whereas staining was less intense in the follicular variant of papillary thyroid carcinoma and in follicular (60 and 75%, respectively) and poorly differentiated carcinomas (28.6%); it was expressed focally and weakly in follicular adenoma cases and even more weakly in the reactive follicular epithelium of nodular goiter (P<0.5). Membrane β-catenin expression was decreased in only two of 13 (15.4%) adenomas and in 21 of 38 (55.3%) carcinomas (P<0.5). Among carcinomas, reduced membrane β-catenin was associated with progressive loss of tumor differentiation and increased invasiveness (P<0.5). The mean nuclear diameter and the mean nuclear perimeter were higher in undifferentiated carcinomas when compared with other subtypes and were the least for follicular neoplasms. Conclusion: Galectin-3 immunostaining and analysis of β-catenin dysregulation may be useful as an adjunct to distinguish benign from malignant thyroid lesions. Quantitative estimation of nuclear features can play a role in assessment of the morphological features and thus help in the diagnosis of thyroid lesions.