CD79B is a critical component of the B-cell receptor (BCR) complex required for BCR signal transduction initiation 1. Working cooperatively with CD79A, CD79B facilitates phosphorylation cascades that lead to BCR internalization, trafficking to late endosomes, and antigen presentation 1. CD79B expression is predominantly restricted to B cells and B-cell neoplasms, appearing early during B-cell development before immunoglobulin heavy-chain rearrangement and persisting longer than CD20 in B-cell differentiation 1. CD79B mutations are particularly significant in diffuse large B-cell lymphoma (DLBCL) pathogenesis. Somatic mutations in the immunoreceptor tyrosine-based activation motif (ITAM) signaling modules of CD79B occur frequently in activated B-cell-like (ABC) DLBCL, with approximately 18% of cases harboring mutations in the first ITAM tyrosine residue that increase surface BCR expression and attenuate feedback inhibition 2. These mutations establish chr17 active BCR signaling as a pathogenic mechanism in ABC DLBCL 2. CD79B mutations also occur frequently in primary CNS lymphoma and CD5-positive DLBCL, often co-occurring with MYD88 mutations 34. Clinically, CD79B is a therapeutic target for antibody-drug conjugates like polatuzumab vedotin in relapsed/refractory B-cell lymphomas, and BCR signaling inhibitors targeting CD79B-dependent pathways show efficacy particularly in mutated ABC DLBCL 56. Mutations in CD79B define a subset of lymphomas highly dependent on BCR signaling for survival.