Histogenetic model for HIV-associated lymphoproliferative disorders infected by EBV (Carbone et al21 and this study). The proposed model is based on the expression pattern of BCL-6 and CD138/syn-1 throughout physiologic B-cell differentiation. B cells within the GC display the BCL-6⁺/syn-1⁻phenotype, whereas B cells that have exited the GC and further matured toward the plasma cell stage exhibit the BCL-6⁻/syn-1⁺ phenotype. On these bases, HIV-associated systemic non-Hodgkin’s lymphomas displaying the BCL-6⁺/syn-1⁻ phenotype, ie, HIV-associated small noncleaved cell lymphoma (HIV-SNCCL) and HIV-associated large noncleaved cell lymphoma (HIV-LNCCL), are postulated to originate from GC B cells. Conversely, HIV-associated lymphomas displaying the BCL-6⁻/syn-1⁺ phenotype, ie, HIV-associated immunoblastic plasmacytoid lymphoma (HIV-IBPL) and HIV-HD, are postulated to derive from B cells that have transited through the GC and have undergone preterminal differentiation. The post-GC nature of these lymphomas is formally documented, at least in the case of AIDS-IBPL, by the association with genotypic markers of GC transit, namely somatic hypermutation of Ig genes and mutations of BCL-65′ noncoding regions. The BCL-6⁻/syn-1⁺phenotype is permissive for expression of the EBV-encoded LMP1 antigen. Conversely, LMP1 expression is consistently absent among HIV-associated lymphomas displaying the BCL-6⁺/syn-1⁻phenotype.