Human immunodeficiency virus (HIV) down-modulates the T-Cell functions, induces polyclonal B-cell activation and is associated with the appearance of lymphomas in patients infected by HIV either in the presence or in the absence of coinfecting Epstein Barr Virus (EBV). The pathogenetic role of HIV in the appearance of lymphoproliferative disorders is yet poorly understood and its presence in tumour cells is not demonstrated. Because of the close similarities to human malignancies, we used the simian immunodeficiency virus (SIV)-macaque animal model to study the pathogenesis of SIV-associated malignancies. In addition to explore the SIV-B cell interactions an in vitro model was established by using immortalized simian B-cell lines. We demonstrate that infectious SIV is present in tumour cells of T- and B-Cell lymphomas arosen in infected monkeys. Of importance simian B cells are susceptible to an in vitro CD4/CCR5/CXCR4-independent SIV infection. This infection leads to the upregulated expression of CD23 and CD40 cell surface markers in the absence of reactivation of simian EBV-like virus. These findings favour the hypothesis that SIV is involved in the process of B- or T- lymphomagenesis occurring in simian acquired immunodeficiency syndrome.