Plasmablastic lymphoma (PBL) is an uncommon but aggressive subtype of diffuse large B-cell lymphoma (DLBCL) that is mostly seen in HIV positive patients. This case report details an HIV-positive patient with two unusual sites of PBL manifestation, the pleural space and the rectum. The patient was initiated on treatment but subsequently developed complications leading to the inability to temporarily continue therapy. In addition to illustrating less common site manifestations of PBL as well as its therapeutic challenges, this case also exhibits how a patient’s socioeconomic and health insurance status can contribute to treatment delays, and hence their overall prognosis and survival.