The epidemic of acquired immunodeficiency syndrome (AIDS) has made an enormous impact in the practice of medicine within the past decade. Of the many associated problems, the increasing frequency of human immunodeficiency virus (HIV)-related malignancies, particularly lymphoma, has been both a fascinating area of study and a most difficult clinical condition to manage. This study investigates lymphoma of the head and neck with clinical studies, as well as immunohistochemical assessments from individual patients. Lymphomas of the head and neck, as they present to the otolaryngologist, can present difficult and challenging diagnostic and therapeutic dilemmas. It is well-known that a significant number of acquired immunodeficiency patients present initially with symptoms related to the otolaryngology field; it was also found that a certain number of lymphomas in the head and neck in HIV+ patients are the initial presentation. In addition, the associated disorders, such as related infections and synchronous additional neoplasms, are described. Also presented are recommendations for diagnosis and work-up of these conditions, based on the experience. In addition, the study of lymphoma as a neoplasm from the molecular biology viewpoint and its course in the immunodeficient state have been important areas of study in an effort to dissect the progression to oncogenesis. The rapidly expanding literature base in this area is discussed.