In the REAL classification system, follicular lymphomas (FL) were subdivided into three grades depending on the number of blasts (6). In this study, we were interested in defining biological parameters possibly being important in the delineation of subgroups. Between 1990 and 1998, biological and cytogenetic investigations were performed on 91 FL. Clonal aberrations were found in all cases. The tumours were subclassified according to the blast content and the morphology of the centrocytes into 29 FL 1, 33 FL 2, 15 FL 3, and 14 FL 3 with a diffuse large B-cell lymphoma component (FL 3 + DLBL). They were characterised by classical cytogenetics, for their mitotic (MI) and proliferative (PI) indices, and CD10, bcl-2, and p53-expression. In contrast to FL 1 and FL 2, which showed a common genetic background with t(14;18), and only differed by their blast content and MI/PI, FL 3 (with or without associated DLBL) turned out to be an inhomogeneous group. 11 follicular lymphomas (with > 150 blasts/10HPF) still showed maturation to centrocytes. They were positive for CD10 and harboured the t(14;18) in 73%. These cases correspond to a "high grade" variant of centroblastic-centrocytic lymphoma according to the Kiel classification (FL 3a). In 18 cases with a follicular or follicular and diffuse growth pattern, the infiltrate consisted of centroblasts exclusively. These tumours were CD10+ in only 50% and were t(14;18)+ in only 22%. Secretory differentiation (clg+) was found in 44%. They were--with respect to primary and secondary chromosome aberrations--more comparable to a follicular variant of DLBL and hence, correspond to centroblastic lymphoma, follicular or centroblastic lymphoma, follicular and diffuse according to the Kiel classification (FL 3b). By histomorphological, biological and cytogenetic investigations, therefore, FL 3 can be delineated into two different biological subgroups with obviously different transformation pathways.