Lymphoplasmacytic lymphoma (LPL) remains a poorly defined entity, even with the discovery of MYD88L265P mutations and association with Waldenström macroglobulinemia (WM). Among bone marrow (BM)-based, low-grade B-cell lymphoma with plasmacytic differentiation (LGBLPD) and immunoglobulin M (IgM) paraproteins, we sought to determine whether MYD88L265P defines a distinct entity and can help refine diagnostic criteria for LPL.