Translocations of the histone-lysineN-methyltransferase 2A (KMT2A) gene, formerly known as myeloid lymphoid leukemia/mixed-lineage leukemia gene, are commonly associated with high-riskde novoor therapy-associated B-cell and T-cell lymphoblastic leukemias and myeloid neoplasms. Rare B-cell non-Hodgkin lymphomas harboringKMT2Atranslocations have been reported, but information regarding the clinical behavior of such cases is limited. Here, we describe two extranodal diffuse large B-cell lymphomas (DLBCLs): a primary thyroid DLBCL and a large cell transformation of a splenic marginal zone lymphoma, which displayed complex karyotypes and translocations involving chromosome 11q23 targeting theKMT2Agene. The pathological and clinical characteristics of these cases are discussed in the context of previously reported lymphomas associated with different types ofKMT2Agenetic aberrations. In contrast to the poor clinical outcomes of patients with acute leukemias and myeloid neoplasms associated withKMT2Atranslocations, patients with B-cell non-Hodgkin lymphomas, exhibiting similar translocations, appear to respond well to immunochemotherapy. Our findings add to the growing list of histone methyltransferase genes deregulated in DLBCL and highlight the diversity of mechanisms, altering the function of epigenetic modifier genes in lymphomas.