We report 2 cases of B-cell lymphoma of the thyroid in which although a marginal zone distribution of the neoplastic cells was present, the cytologic features of the cells indicated large cell lymphoma. One of the cases showed an accumulation of crystalline inclusions within the cytoplasm of the neoplastic cells. Many of these inclusion-bearing cells showed plasmacytoid features. By immunohistochemical studies performed on formalin-fixed paraffin-embedded tissue, both of the cases showed a B-cell phenotype as indicated by CD20 expression, and 1 showed kappa light chain restriction. In both cases, Ki-67 staining corroborated the impression of an aggressive neoplasm with staining of 50% and 90% of the tumor cells. Both patients received cyclophosphamide, doxorubicin, vincristine, and prednisone with radiation therapy, and both are without evidence of disease after 17 and 18 months of follow-up. It is important to recognize this pattern of large B-cell lymphoma of the thyroid gland. While the indolent course typical of most low-grade extranodal marginal zone lymphomas is not likely in these cases, the outcome may be favorable if patients are treated aggressively with therapy for large cell lymphoma.