A 22-year-old man with HIV infection (CD4+ count 563/mm3 and HIV-1 load 186 copies/mL) presented with headache and left diplopia. On examination, ipsilateral proptosis with extraocular movement impairment in all directions was noted (Figure, A, and Video 1). Brain MRI revealed a diffuse pattern with an infiltrative left orbital lesion (Figure, B–D) and the subgaleal biopsy revealed plasmacytoma. HIV may act as a superantigen, triggering B-cell clonal expansion. However, there is little evidence to support the development of multiple myeloma.1,2 Plasma cell disorders are rare in patients with HIV; they tend to occur early in the course of infection and are clinically aggressive.