We report the case of a middle-aged HIV-positive man who presented with proptosis and retro-ocular pain. On CT and MR imaging, a retro-orbital enhancing mass was seen, and PET/CT revealed this lesion as well as a similarly characterized mass in the nasopharynx to be hypermetabolic. Biopsy and subsequent pathological characterization revealed this mass to be plasmablastic lymphoma (PBL), a rare form of non-Hodgkin's lymphoma associated with HIV-infection. PBL is a diffuse B-cell lymphoma with characteristic cell marker patterns. The most common site of this malignancy is within the oral cavity. This case constitutes an unusual orbital manifestation of plasmablastic lymphoma as well as an unusual case in its response to chemotherapy. This case illustrates the importance of functional imaging with PET/CT in the diagnosis, management, and follow-up of plasmablastic lymphoma.