Individuals who are immunodeficient, including those who are HIV infected, have an increased risk of developing lymphoproliferative disorders (LPDs). These lesions in the HIV-infected patient population are somewhat heterogeneous, but are more often clearly benign or malignant than the LPD lesions that arise in other immunodeficient states. Like those occurring in the setting of posttransplantation (also see Chap. 28, methotrexate therapy, primary immune disorders and advanced age, the AIDS-related LPDs are often associated with herpesvirus infection, particularly Epstein–Barr virus (EBV; HHV-4) and Kaposi sarcoma herpesvirus (KSHV; HHV-8). Also similar to the other immunodeficiency-related lymphoproliferations, if the HIV positive patient’s immune status can be restored, such as by highly active antiretroviral therapy (HAART), the lesions may regress. However, in many instances, a secondary genetic alteration, not all of which have been characterized, has occurred resulting in transformation to an irreversible neoplastic process.