One hundred fourteen patients with advanced (stage III or IV) epidermoid carcinoma of the oral cavity, pharynx, larynx, and hypopharynx were treated by surgery and postoperative radiation therapy between 1975 and 1980. Twenty-seven patients also received preoperative platinum-containing chemotherapy. Sixteen patients developed second malignant neoplasms. The site of the second malignant neoplasm was in the esophagus in seven patients (44%), in the lung in six patients (37.5%), and at other sites in three patients (18.5%). Relapse of the head and neck cancer (at the primary site in 6 patients, in the neck in 11 patients, and at distant sites in 20 patients) appeared within the first 2 years in virtually all cases. In contrast, second malignant neoplasms have appeared at a steady rate of approximately 6% per year, for at least the first 4 years. Future efforts at improving the survival of patients with advanced head and neck cancer, therefore, must include strategies aimed at decreasing the incidence and the morbidity and mortality from second malignant neoplasms.