A prospective clinicopathologic study of the nasopharyngeal lymphatic tissue, using a standardized approach, was carried out in 66 patients infected with human immunodeficiency virus (HIV) in Aviano, Italy. Two hundred eighteen patients without HIV infection served as a control group. A significantly higher percentage of nasopharyngeal lymphatic tissue hypertrophy was observed in HIV-infected patients compared with the control group, both clinically and pathologically. The finding of a higher incidence of nasopharyngeal lymphatic tissue hypertrophy during some stages of the disease, when cervical lymph nodes are enlarged, suggests that the extranodal nasopharyngeal district behaves in the same way as the lymph nodes. Nasopharyngeal lymphatic tissue hypertrophy should be placed at the forefront of the hitherto known head and neck manifestations of HIV infection. An ear, nose, and throat examination is mandatory for all patients with known or suspected HIV infection.