Histiocytic medullary reticulosis represents a proliferation of malignant histiocytes which produce pancytopenia through marrow involvement and the phagocytosis of granulocytes, leukocytes and platelets. The disease is typically characterized by a fulminant febrile course which results in death from a variety of complications due to pancytopenia or intercurrent infections. Its diagnosis is based on bone marrow aspiration or tissue section in which large histiocytes can be demonstrated phagocytizing red or white blood cells and platelets. Therapy has included irradiation, steroids, antibiotics, antimetabolites, and the like, but with poor results. Two patients with head and neck manifestations of histiocytic medullary reticulosis are described in detail. It is felt that refinements in diagnosis must still be made,, since any patient survival may well be predicated by the early initiation of aggressive cytotoxic therapy.