DLBCL cases that do not fit the distinctive clinical presentation, tissue morphology, neoplastic cell phenotype, and/or pathogen-associated criteria of other DLBCL subtypes are termed Diffuse large B-cell lymphoma, not otherwise specified: DLBCL, NOS, while representing 80–85% of all DLBCL cases, is a diagnosis of exclusion. In general, DLBCL, NOS is an aggressive disease with an overall long-term survival rate in patients treated with standard chemotherapy regimens of ~65%. However, this disease has many variants that differ not only in the just cited parameters but also in their aggressiveness and responsiveness to treatment.