Follicular lymphoma (FL) grades 1 and 2 are regarded as a distinct disease entity, whereas data suggest that FL grade 3 might be an inhomogeneous tumor category. To define the biologic spectrum of FL, 89 follicular lymphomas were studied for their cytologic composition, antigen expression, mitotic and proliferation indices, cytogenetics, and clinical data. In contrast to the homogeneous appearance of FL grades 1 and 2 (29 and 33 cases, respectively), 2 types of FL grade 3 were recognized. Eleven cases of FL 3a displayed structural features similar to those of FL 1 and 2 and were composed of centroblasts and centrocytes, whereas 16 cases of FL 3b, with (n = 4) or without (n = 12) a diffuse large B-cell lymphoma component (DLBL) (FL 3b +/- DLBL), consisted exclusively of blasts. In contrast to FL 3a, FL 3b +/- DLBL were CD10(+) in only 50% of cases and displayed plasmacytoid differentiation in 44% of cases. Although FL3a was t(14;18)+ in 8 of 11 (73%) cases, only 2 of 16 (13%) FL3b +/- DLBLs harbored this translocation. In contrast, chromosomal breaks at 3q27 were encountered in 7 of 16 (44%) FL 3b +/- DLBL in contrast to only 2 of 11 (18%) FL 3a, and the spectrum of secondary aberrations in FL 3b +/- DLBL was similar to that of diffuse large B-cell lymphoma. We conclude, therefore, that FL grade 3 is a heterogeneous disease group and that the distinction proposed in the new World Health Organization classification between FL 3a (with centrocytes) and FL3b (without centrocytes) is of biologic, and possibly clinical, importance.