BCL6 is a transcriptional repressor whose deregulated expression plays a key role in diffuse large B-cell lymphomas (DLBCLs). BCL6 expression characterizes one of the two main subtypes (GC type) of DLBCL, while the other (ABC type) is recognized by increased NFκB activation. The mechanistic basis of this distinction remains unclear and the BCL6 targets have been only partially explored. Here we describe how NFκB activity is increased after BCL6 silencing by shRNA in DLBCL cells, leading us to propose that BCL6 represses NFκB activity. We also demonstrate that this repression is brought about by a mechanism involving protein–protein interaction between BCL6 and NFκB members, both in vitro and in vivo. Analysis of a series of DLBCLs shows a negative correlation between the expression of NFκB target genes and BCL6. This combined approach using silenced cells and a series of human DLBCL samples leads us to a better understanding of the role of BCL6 as an NFκB regulator in B-cells. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.