Main viral and molecular pathogenic pathways. Lymphomas in patients infected with HIV are heterogeneous, not only pathologically but also in terms of pathogenetic pathways and cellular derivation. The molecular pathway in HIV-associated BL involves activation of MYC (100% of cases), inactivation of p53 (50%-60% of cases), and infection by EBV (30%-50% of cases). Unclassifiable lymphomas with features intermediate between BL and DLBCL may occur. Molecular studies have shown rearrangements in BCL2 (and BCL6) and MYC genes. The molecular pathogenesis of HIV-associated centroblastic (CB) and immunoblastic (IB) DLBCL is complex and more heterogeneous. Infection with EBV occurs in 30% of DLBCL with CB morphology and 90% of DLBCL with IB and anaplastic (ALCL) morphology. Many EBV-positive IB DLBCLs express the EBV-encoded transforming protein LMP-1. There is an association between molecular changes in the BCL6 proto-oncogene and 20% of HIV-associated CB DLBCLs. Molecular studies of cells in PEL have shown no rearrangements in BCL1, BCL2, BCL6, and MYC genes. However, mutations in the BCL6 5′ noncoding region are common in PEL. In addition to consistent infection by KSHV, PELs are also commonly infected by EBV (80%). Regarding the molecular pathogenesis of PBL of the oral cavity type, EBV infection of the neoplastic clone has been frequently reported. In HIV-infected patients, nearly all cases of cHL are associated with EBV infection and express LMP-1.