Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkins lymphoma of the central nervous system and eye. It is over 1000 times greater in HIV positive than in non-HIV populations. The decline in its incidence since the introduction of the highly active anti-retroviral therapy (HAART) suggests an association of this tumor with severe and prolonged immunosuppression. Clinical presentation results from neurological deficits related to the site of the tumor. Systemic B symptoms are also common. The detection of EBV DNA from the CSF, by nested PCR, is a highly sensitive and specific for HIV-related PCNSL. We present the case of a 31-yearold African American man with medical history significant for AIDS who presented with one-month history of lack of energy and somnolence. CSF appearance was normal. MRI suggested primary CNS lymphomas or toxoplasmosis. CSF EBV DNA by PCR was found to be positive. The clinical presentation of PCNSL is similar to that of toxoplasmosis encephalitis in patients diagnosed with HIV. The initial differentiation between the two pathologies on presentation is important since treatment differs and early treatment has been shown to reduce mortality.