The serologic and clinical features of a 32-year-old women with coexistent systemic lupus erythematosus and lymphoma were studied. A cervical node biopsy specimen demonstrated nodular, poorly differentiated lymphocytic lymphoma; subsequent development of polyarthralgias prompted evaluation for connective-tissue disease, and a high titer of antinuclear antibody was found. Immunochemical studies proved that this antibody was directed to the Sm antigen, a serologic finding highly specific for systemic lupus erythematosus. This antibody has been maintained throughout the course of the patient's disease, characterized by persistent lymphadenopathy, pleuropericarditis, arthritis, hypocomplementemia, hyperglobulinemia, and a slight elevation of titers of anti-DNA antibody. The course of the lymphoproliferative disorder has been consistent with that of an indolent non-Hodgkin's lymphoma. In sera from other patients with lymphoproliferative disorders, anti-Sm antibody was not found. These findings emphasize the importance of establishing the antigenic specificity of antinuclear antibodies detected in the sera of patients with neoplasia.