Salivary gland disease is an important manifestation of HIV-infection. The aim of this study was to evaluate the cytologic findings of salivary gland fine needle aspiration (FNA) in South African human immunodeficiency virus (HIV)-infected patients. A retrospective review was performed on confirmed HIV-positive patients who underwent FNA of various body sites, including salivary glands, over a 5-year period. There were 495 (14.1%) salivary gland FNAs out of a total of 3,501 HIV-positive patients. This included 260 (52.5%) parotid, 226 (45.7%) submandibular, 2 (0.4%) sublingual, and 7 (1.4%) specimens labeled as a salivary gland aspirate, exact site not provided. Patients were of average age 34 years (range 9 months to 63 years) with a female: male ratio of 1:0.6. There were 37 (7.5%) inadequate FNAs and 22 (4.4%) that contained normal gland constituents only. Most diagnoses were benign and comprised 168 (33.9%) reactive lymphadenopathy, 115 (23.2%) benign lymphoepithelial cysts, 62 (12.5%) mycobacterial infections, and 52 (10.5%) abscesses, of which 10 had associated mycobacterial infections. Neoplasms accounted for 31 (6.7%) diagnoses including 11 pleomorphic adenomas, 13 lymphoma, 3 Kaposi sarcoma, 1 squamous cell carcinoma, 1 metastatic carcinoma, and 1 rhabdomyosarcoma. There were four epidermoid inclusion cysts, three non-specific sialadenitis, one mucocele, and one spindle cell lesion not able to be further characterized. FNA is a useful procedure to evaluate salivary gland lesions in an HIV-infected population, allowing prompt management to be undertaken and obviating the need for surgery in many instances, an important consideration in an underfunded public health care system.