Translocations involving band 3q27, affecting the major breakpoint region (MBR) of BCL6, are common in diffuse large B-cell lymphomas (DLBCLs). Recent data suggest an alternative breakpoint cluster region (ABR) located between 245 and 285 kb 5′ of BCL6, which might be associated with Follicular Lymphoma (FL). Ten DLBCLs and 9 FLs grade 3B with cytogenetic rearrangements at 3q27 were studied by fluorescence in situ hybridization (FISH) to discriminate between breakpoints at the ABR and MBR. Eight DLBCLs contained a breakpoint in the MBR, and 6 FL grade 3B (FL3B) cases contained a breakpoint in the ABR. No specific chromosomal partners could be identified in both groups. Previously published data have suggested that FL3B cases with 3q27 aberrations are closely related to the majority of DLBCLs of germinal center cell origin. However, our findings suggest that the mechanism of 3q27 rearrangement in FL3B cases is similar to the mechanism in follicular lymphomas grade 1,2, and 3A cases. © 2005 Wiley-Liss, Inc.