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Patients with acquired immunodeficiency syndrome (AIDS) are at an increased susceptibility to pathogens and associated malignancies which can present with a unique constellation of symptoms. In this article, we describe a case of Castleman disease in a patient with AIDS, nonadherent with antiretroviral therapy (ART), who presented with fevers, constant abdominal pain, nausea, and vomiting. After an extensive work up, a lymph node biopsy confirmed a diagnosis of human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease. Patients presenting with AIDS and fever have broad differential diagnoses; therefore, reaching a diagnosis as rare as Castleman disease can be challenging. HHV-8 has a propensity to CD20 positive B cells, which allows rituximab to be an effect treatment.