Immunophenotypic analysis is useful in distinguishing reactive from neoplastic lymphoproliferations, particularly when tissue is limited or histologic findings are equivocal. Surface membrane immunoglobulin (SmIg) light chain restriction in B cells is especially helpful in documenting clonality, and the loss of SmIg by B cells in extramedullary sites also has been used as a criterion to support the presence of lymphoma. However, we identified 3 cases of benign follicular hyperplasia (in 101 cases analyzed) with profound expansions (56%-88% of the B cells) of SmIg light chain-negative B cells without clonality by immunoglobulin heavy chain gene polymerase chain reaction. Thus, although uncommonly encountered, lack of SmIg light chain expression by B cells should not necessarily be interpreted as indicative of lymphoma. Interestingly, 2 of the 3 patients with these "aberrant" expansions were HIV+, and such patients are at heightened risk for the development of lymphoma. Therefore, there is the potential for misdiagnosing lymphoma if flow cytometric data are interpreted inappropriately in isolation.