Strikingly, a gain-of-function oncogenic somatic mutation in MyD88 is causative of aggressive hematologic malignancies [7,16,17,18], including activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL; ~39% of total cases) [4], Waldenstrom’s macroglobulinemia (WM; ~95% of total cases), and primary central nervous system (CNS) lymphoma [8]. The gene discussed is MYD88; the disease is diffuse large B-cell lymphoma.