Objectives: In fall 2004, the authors used a survey to assess the knowledge, attitudes, motivations, and behaviors of college students relative to oral cancer prevention to inform development of targeted prevention programming. Participants: A convenience sample of 1,003 undergraduate students at one public university in Indiana participated. Methods: Discriminant function analysis was employed to analyze participants' motivations; perceived risks; individuals who influence participants' alcohol, tobacco, and marijuana use; and factors that facilitate and discourage use. The study sample was divided into users and nonusers to differentiate between groups and predictor (discriminating) variables. Multiple regression analysis was used to determine the extent to which participants' knowledge, attitudes, peer perceptions, sex, age, and ethnicity contributed to participants' combined alcohol, tobacco, and marijuana use behaviors. Results: With 2 exceptions, discriminant function analysis (p less than 0.01) correctly categorized user status (ie, nonusers vs combined users of alcohol and cigarettes; nonusers vs combined users of alcohol, cigarettes, and marijuana) by the predictor variables. Multiple regression analysis to determine whether independent variables predicted combined drug use generated significant (p less than 0.01) results across all combined use behaviors. Conclusions: Multiple oral cancer prevention program options along with additional formative research efforts were suggested by study results.