Galectin-3 is a 31 kD beta-galactoside-binding lectin which is expressed by several types of non-neoplastic and neoplastic cells and which may be involved in cell-extracellular matrix interactions. An immunohistochemical study has been made of the expression of galectin-3, as well as its ligand, laminin, in a spectrum of benign and malignant thyroid neoplasms and in some non-neoplastic conditions. Immunohistochemistry with anti-human recombinant galectin-3 antibody showed consistent, intense positivity in the neoplastic cells of 18 cases of papillary carcinoma and less intense staining in the five anaplastic carcinomas studied. In addition, two out of three poorly differentiated carcinomas, three out of six medullary carcinomas, and four out of eight follicular carcinomas had less intense or focal positivity. One case of Hürthle cell carcinoma showed scattered strongly positive cells. Eight follicular adenomas, three hyperplastic nodules, five nodular goitres, and normal thyroid tissue were negative. Galectin-3 mRNA expression was also evaluated in three of the papillary carcinomas, two follicular adenomas, and one hyperplastic nodule with matched normal tissue. Northern blot analysis demonstrated mRNA overexpression in the three cases of papillary carcinomas, whereas normal and benign tissues were negative. Laminin distribution in neoplastic and non-neoplastic tissue varied with architectural patterns but did not correlate with galectin-3 immunohistochemical expression. We conclude that expression of galectin-3 is limited to inflammatory foci in normal and benign thyroid tissue and is a phenotypic feature of malignant thyroid neoplasms, especially papillary carcinomas.