A close relationship between Hashimoto thyroiditis (HT) and low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) has been shown. We used immunohistochemistry to study paraffin sections from 40 unselected cases of HT and scored cases according to the lymphoid infiltrate and presence of lymphoepithelial lesions (LELs). Clonality was assessed by kappa/lambda immunohistochemistry and polymerase chain reaction for immunoglobulin heavy chain gene rearrangement (IgH PCR). Histologic findings were compared with 2 cases of primary thyroid MALT-type lymphoma. In HT, the lymphoid infiltrate consisted predominantly of T cells in all cases; B cells, associated with germinal centers, did not have the appearance of marginal zone cells. All cases had identifiable T-cell LELs; immunohistochemistry confirmed inconspicuous, rare B-cell LELs in 13 of 40 cases. In all cases, plasma cells were polyclonal and IgH PCR showed a polyclonal pattern. Clinical follow-up was available for 34 patients. Lymphoma developed in none. In contrast, a B-cell predominant infiltrate of marginal zone cells was present in the MALT-type lymphomas that was not confined to germinal centers. Cytokeratin stains demonstrated severe loss of epithelial elements and destructive LELs. LELs are not, in isolation, a useful criterion for distinguishing low-grade MALT-type lymphoma of the thyroid from HT. Features associated with low-grade MALT-type lymphoma include a predominance of B cells, marked loss of epithelial elements, and destructive LELs composed of marginal zone B cells. Unselected cases of HT do not contain monoclones detectable by IgH PCR.