High-grade carcinoma of the oral cavity is considered to be an aggressive malignancy associated with a poor prognosis. The tumors are often considered to be relatively radiosensitive. Because previous reviews of oral cavity cancer have contained few patients with grade 4 lesions, little is known about the true behavior of these tumors. Information was collected on 80 patients with high-grade carcinoma of the oral cavity to determine the clinical findings and optimal treatment of this tumor. Primary tumor location, presence of neck metastasis, and clinical stage did not affect survival. Tumor size was a significant risk factor. The 5-year survival rate for patients with high-grade carcinoma treated by combination surgery and radiation (52%) was significantly greater (p less than or equal to 0.05) than that for patients treated by radiation alone (28%) or surgery alone (24%). This study is the first to describe the clinical course of a large number of patients exclusively with high-grade carcinoma of the oral cavity.