DLBCL carrying rearrangements of MYC and B-cell lymphoma 2 (BCL2) genes and/or B-cell lymphoma 6 (BCL6), detected by fluorescence in situ hybridization (FISH), were introduced in the 2017 World Health Organization (WHO) classification update as defining alterations of a novel category named “High Grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements”, known to poorly respond to R-CHOP. This evidence concerns the gene BCL2 and diffuse large B-cell lymphoma.