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. 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. 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. 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.