Multiple myeloma is a biologically diverse, malignant disease that involve plasma cells. Multiple myeloma is characterized by the unrestrained proliferation of monoclonal plasma cells within the bone marrow. In the present case report, the case of a human immunodeficiency virus (HIV) positive patient with an initial manifestation of extramedullary myeloma involving the parotid gland is described. The patient had been on antiretrovirals for the last two years. A Medline, Embase, Scopus and Google Scholar search was performed using the key words: ‘Parotid extramedullary myeloma AND HIV’ as part of the literature review. A 46-year-old female presented to our hospital with a 6-month history of a painful mass on the left side of the face, involving the parotid area, with rapid growth in the preceding month. There was associated fever, body pains and difficulty opening the mouth. This resulted in difficulty in mastication and she also reported pain on swallowing. She did not notice any weakness of her face on the left side. She had no complaints regarding her eyes, such as visual disturbances, eye pain, or an inability to close the eye on the affected side. The patient was diagnosed with HIV infection 2 years prior and had been on highly active antiretroviral therapy (HAART) since the diagnosis. There is no consensus regarding a treatment protocol for HIV positive patients on HAART and multiple myeloma. However, based on the clinical case report and a review of the relevant literature, the treatment should include high doses of a combination of chemotherapeutic agents. Although multiple myeloma is considered incurable, all patients should be started on treatment with the goal of preventing further complications.