Heterozygous gain of function mutations, preferentially affecting the EZH2 SET domain at the Y641 residue and making EZH2 more efficient at H3K27 trimethylation (97), are found in up to 30% of GCB-DLBCL and FL and de facto enriched in EZB/C3 DLBCL subtype (18, 89, 98). The gene discussed is EZH2; the disease is diffuse large B-cell lymphoma.