High-grade B-cell lymphomas (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements (i.e. "double-hit" lymphomas; DHL; 6–9% of aggressive B-cell lymphomas) and the subset of diffuse large B-cell lymphomas (DLBCL) and HGBCL, not otherwise specified (NOS), with MYC and BCL2 protein over-expression (i.e. "double-expressor" lymphomas; DEL; 25–30% of remaining aggressive B-cell lymphomas) represent distinct but overlapping subsets of mature B-cell non-Hodgkin lymphomas with aggressive clinical course, poor response to conventional chemotherapy (i.e. R-CHOP) and high relapse rates [1, 2]. The gene discussed is BCL2; the disease is B-cell non-Hodgkin lymphoma.