In order to define the clinical behavior and characteristics of oral and oropharyngeal squamous cancer in nontobacco users, 40 surgically treated American Joint Commission (AJC) stage I and II tumors in 36 nontobacco-using patients were retrosepctively compared with 306 similarly staged and treated tumors in 286 tobacco-using patients. Significantly more nontobacco-associated tumors were found in females (P less than 0.005) whose mean age was significantly greater than that of tobacco users (P less than 0.001). Nontobacco users had proportionately more tumors of the buccal mucosa, oral tongue, and hard palate and fewer of the floor of mouth (P less than .025). There was no difference in the distribution of histologic grades between the two groups. The incidence of initial or subsequent nodal disease and the incidence of second upper aerodigestive tract cancers were similar. Despite similar rates of failure of initial treatment, the mean time to failure was significantly greater in nontobacco users (P less than 0.01). There was no difference in determinate 5-year survival between the two groups. Oral and oropharyngeal cancers in nontobacco users are no more aggressive than similar lesions in tobacco users.