BACKGROUND The differential diagnosis for a parotid mass is broad, including infectious, autoimmune, and neoplastic etiologies. In people with HIV, regardless of viral suppression or immune status, neoplastic causes are more common. This report describes the evaluation of a woman with a large parotid mass, with an ultimate diagnosis of multiple myeloma with extramedullary plasmacytoma. CASE REPORT A 51-year-old woman with HIV infection presented with headache, weight loss, and right facial mass that was present for 5 years but more rapidly enlarging in the prior year. CD4 count was 234 cells/mL, and HIV RNA was 10 810 copies/mL. Physical examination was significant for a large deforming right-sided facial mass, decreased sensation in the V1 and V2 distributions, and right-sided ophthalmoplegia and ptosis. MRI and PET/CT scan confirmed a metabolically active large parotid mass with extension into the cavernous sinus. An IgG kappa monoclonal spike was present on serum protein electrophoresis. Incisional biopsy of the facial mass showed atypical lymphoid cells with plasmablastic and plasmacytic morphology with a high mitotic rate and proliferation index. She was diagnosed with R-ISS stage II IgG kappa multiple myeloma with extramedullary plasmacytoma, and initiated on chemotherapy, radiation, and antiretroviral therapy. CONCLUSIONS A rapidly enlarging parotid mass should prompt timely evaluation and biopsy for definitive diagnosis, particularly in immunocompromised patients, including people with HIV. Extramedullary plasmacytomas have a more aggressive disease process in people with HIV and are associated with high-risk multiple myeloma and progression, as seen in this patient.