Background: Idiopathic CD4+ lymphocytopenia (ICL) is a rare disorder in which patients have mild and/or severe opportunistic infections or maybe without symptoms. The etiology is currently unknown. Diagnosis is made by excluding retroviral infections (human immunodeficiency virus-1 or -2, human T cell lymphotropic virus-1 or -2) or other known causes of immunosuppression. Objective: To provide a case report of a patient with possible ICL who presented with a rare form of primary non-Hodgkin lymphoma (NHL) of the central nervous system (CNS). Review of the literature has identified only five other patients with NHL and ICL; however, none of these had a CNS lymphoma. Results: We describe a patient with possible ICL, and address links between lymphopenia and lymphoproliferative disorders. Conclusions: Although not uncommon for patients infected with human immunodeficiency virus to develop CNS NHL, this is the first case of a possible ICL patient with such a lymphoma. This case revisits an important relationship between lymphopenia and lymphoproliferative disorders.