Diffuse large B-cell lymphoma (DLBCL) comprises a diverse group of neoplasms that have recently been subdivided by gene expression profiling and immunohistochemical studies into at least 2 subgroups [germinal center (GC) type and non-GC type]. The non-GC subtype has a post-GC activated phenotype and typically expresses MUM1 by immunohistochemistry. We hypothesized that MUM1 may be dysregulated/up-regulated in these tumors by a chromosomal translocation, as is seen in many cases of plasma cell myeloma [where MUM1 is juxtaposed with the immunoglobulin heavy chain gene (IgH)]. Therefore, using a novel MUM1 break-apart probe constructed in our laboratory, we performed fluorescence in situ hybridization on 33 cases of DLBCL (17 GC type and 16 non-GC type) for a MUM1 translocation. We identified 1 case of a MUM1 translocation out of 31 cases with successful fluorescence in situ hybridization. This case was a non-GC DLBCL (1/15). We conclude that genetic abnormalities involving MUM1 are rare in DLBCL and that a mechanism of deregulation of the MUM1 protein other than by a translocation event is involved in the majority of non-GC cases.