Accurate diagnosis of BL and DLBCL is essential because adequate chemotherapy regimen differs between both types of lymphomas. BL is cured by high intensity chemotherapy, whereas DLBCL is usually treated by lower-dose chemotherapy regimens: cyclophosphamide, doxorubicin, vincristine, and prednisone, in association with LEE011 rituximab anti-CD20 antibody. Although Ig-myc translocation is the hallmark of BL, c-myc translocations are also found in other lymphomas. In particular, they are found in a subset of DLBCL and in a high proportion of lymphomas that are borderline between BL and DLBCL and were previously called « atypical BL » or « BL-like lymphoma ». These latter lymphomas are now categorized as « Bcell lymphomas, unclassifiable, with features intermediate between DLBCL and BL », and will be referred to as BL/DLBCL in this study. In BL/DLBCL and DLBCL, c-myc translocations often involve non-Ig partners and are associated with a complex caryotype. Several studies have shown that these cases represent aggressive forms with poor prognosis and the most appropriate treatments remain a matter of debate. In particular, a recent study showed that, among DLBCL patients treated with R-CHOP chemotherapy, those having c-myc gene rearrangements had an inferior prognosis compared to those without c-myc translocations, and it was suggested that treatment regimens similar to those used in BL would be more appropriate for these cases. These observations highlighted the importance of identifying cases of DLBCL with c-myc translocations. However, cytogenetic studies are not systematically performed. In previous immunohistochemical studies, we showed that Epstein-Barr virus -induced gene 3, a molecule related to the p40 subunit of interleukin -12, exhibited a restricted expression profile among B-cell lymphomas. We found that EBI3, which was originally characterized as a gene induced in EBV-transformed B cells by the viral oncogene LMP1, was also expressed in certain non-EBV-associated B-cell lymphomas such as DLBCL. Indeed, EBI3 was found to be expressed by tumoral cells in 18/22 cases of DLBCL, whereas it was not expressed in 6/6 cases of EBV-positive BL, consistent with the absence of LMP1 expression in EBV-associated BL. Subsequently, a study of gene profiling by Dave et al showed that EBI3 was among the NF-kB regulated genes that were selectively overexpressed in DLBCL compared to BL. These observations prompted us to further analyze the expression of EBI3 in large series of BL and DLBCL to clearly establish its differential expression profile among both types of lymphomas, and the usefulness of EBI3 immunohistochemistry for their differential diagnosis. In addition, we investigated whether EBI3 immunohistochemistry could be used as a tool to identify cases with potential c-myc gene rearrangements among BL/DLBCL and DLBCL.