Histiocytosis X may be isolated or generalized in its clinical involvement. Spontaneous resolution may occur, although progression to diffuse systemic disease has also been found. The disease is believed to originate from the mononuclear phagocytic series of cells, although the reason for this activation remains unknown. A possible local reaction to an inciting agent in the nasopharynx or oral cavity has been suggested by the frequent head and neck manifestations in this disease. The prognosis and treatment of patients should be predicated on the staging or extent of disease. Local disease should be treated in a conservative manner. Low dose radiation therapy should be used for inaccessible lesions or lesions in which removal may produce serious morbidity. In the future, randomized treatment protocols need to be undertaken to clarify the status of chemotherapy and immunotherapy in patients with disseminated or aggressive disease.