Mucosa-associated lymphoid tissue (MALT) has recently been recognized as a possible site of origin for low-grade lymphomas of the B-cell type. Though relatively rare, these MALT lymphomas may arise within several sites in the head and neck, and often present diagnostic and therapeutic challenges. We review 4 cases of primary MALT lymphoma of the head and neck, treated with surgical excision (3 cases), irradiation (2 cases), and chemotherapy (1 case), to further characterize this new subtype of head and neck malignancy. The mean time from onset of symptoms to histologic diagnosis was 15 months. Fine needle aspiration identified an atypical lymphoid infiltrate in only 1 of 3 patients. Immunohistochemical analysis was essential in establishing the diagnosis of MALT lymphoma in all 4 of the cases, and demonstrated characteristic negative staining for CD3, CD5, and CD43, positive staining for CD20, and monotypic staining for either kappa or lambda light chain immunoglobulin markers. All patients achieved complete remission after primary therapy, and all remain free of disease with follow-up ranging from 6 to 54 months (mean 33 months). The diagnosis of MALT lymphoma should be considered in cases of atypical lymphoid infiltrates in the head and neck, and increased awareness coupled with detailed immunohistochemical analysis is essential to securing an accurate diagnosis. Clinical remission of MALT lymphoma may be achieved with several modalities, but further study will be required to determine the long-term response to treatment.