A COO-based classification of aggressive B-cell lymphomas. The newly described DZsig (oval), that is defined by a normal germinal center dark zone centroblast profile, identifies a group of DLBCLs that were originally predominantly included in the GCB gene-expression class (yellow). DZsig brings together cases with a dismal outcome (approximately 60% 2-year overall survival). The remaining DLBCL, not otherwise specified (NOS)-GCB-type cases are also distinct and characterized by an excellent outcome (approximately 90% 2-year overall survival). At the DNA level, however, DZsig is heterogeneous, containing approximately one-third lymphomas with concomitant MYC and BCL2 rearrangements (HGBCL-DH-BCL2, mid-oval, orange) and two-thirds without this genetic aberration (lower part of oval, light orange). The genetic composition of the latter group remains to be elucidated. It should be noted that the DZsig gene-expression profile is not specific for DLBCL, however, and extends beyond this entity since it is also a consistent feature of Burkitt lymphoma (top of oval, pink). How DLBCL with concomitant MYC and BCL6 rearrangements (DLBCL-DH-BCL6) may relate to this novel COO classification is not fully resolved.