Primary effusion lymphoma (PEL) is a rare form of high-grade non-Hodgkin's lymphoma that usually occurs in patients with compromised immunity or human immunodeficiency virus (HIV) infection. PEL is a B-cell lymphoma that principally presents as effusions without a tumor mass. We present a case of a 56-year-old African-American male with a medical history of HIV admitted to the hospital with right lung lower lobe pneumonia and parapneumonic effusion. Thoracentesis and pleural fluid cytology led to the diagnosis of PEL. He received treatment with chemotherapy and antiretroviral therapy (ART). The emphasis is to investigate immunocompromised patients presenting with pleural effusion for PEL, as it is a rare ailment with a high mortality rate.