The authors of this study, from the University of Michigan, evaluated the role of induction chemotherapy for patients with stages III and IV resectable oral squamous cell carcinoma. Nineteen patients were initially enrolled in the induction chemotherapy cohort. Patients with clinical or radiographic evidence of bone involvement were excluded. Patients with a response of at least 50% underwent concurrent chemoradiotherapy; those with a response of less than 50% underwent surgical treatment and postoperative radiotherapy. A comparison was made with cohort of patients treated with primary surgery. No difference was noted in age, sex, pretreatment AJCC stage, T and N classifications, smoking status, alcohol consumption, or tumour subsite between induction chemotherapy and surgical cohorts. Median follow-up was 9.4 years in the induction chemotherapy group and 7.1 years in the surgical cohort. The overall survival at five years was 32% in the induction chemotherapy group and 65% in the surgical group. The disease-specific survival was 46% in the induction chemotherapy group and 75% in the surgical group. The locoregional control was 26% in the induction chemotherapy group and 72% in the surgical cohort. Multivariable analysis demonstrated significantly better overall and disease-specific survival and locoregional control outcomes (P = .03, P = .001, and P < .001, respectively) in the surgical cohort. These findings support surgery as the principal treatment for oral squamous cell carcinoma.