We describe 6 cases from the University of Washington Hematopathology Laboratory (Seattle) in which prominent, clonal, follicle center B-cell populations were identified by flow cytometry and confirmed by molecular methods, but in which the histologic features showed reactive follicular hyperplasia without evidence of bcl-2 overexpression or the t(14;18). The 6 cases included 5 lymph node biopsy specimens and 1 tonsillectomy specimen. Of the 6 cases, 5 occurred in young males (8-28 years) with no known immunologic abnormality; the other case was a 32-year-old, HIV-positive woman. In all 6 cases, clonal CD10+ B cells representing at least 20% of the total B cells were identified. Available clinical follow-up ranging from 13 to 56 months revealed no evidence of lymphoma in any of the 6 patients. Our findings add rare cases of follicular hyperplasia to the list of histologically reactive settings in which clonal B-cell populations might be present.