Background: Oral and oropharyngeal cancer are significant health problems. They are both life-threatening conditions usually diagnosed at an advanced stage causing survival rates to decline.Aim: To assess and compare practices, knowledge and attitude regarding oral and oropharyngeal cancer between dental and medical practitioners. Methods: A cross-sectional study was conducted to assess knowledge, attitude and practices of oral and oropharyngeal cancer among dental and medical practitioners at King Abdulaziz Medical City, Riyadh, Saudi Arabia. 360 participants were included in the study using a convenient sampling technique. Participants were approached in their clinics and printed self-administered questionnaire were handed over to them after signing a written consent form. Frequency distribution and Chi-Square test were used for the statistical analysis and the level of significance was set at P value of .05 or less.Results: A total of 174 participants responded. Assessment of oral and oropharyngeal cancer knowledge between dental practitioners and medical practitioners showed comparable results. Regarding practices, a significant difference was seen between medical practitioners and dental practitioners in determining the duration of intraoral ulcer to consider urgent referral (P = .006) and in number of referrals made in relation to suspicious oral lesions (P = .002). Moreover, a significant difference (P = .006) was seen between medical practitioners and dental practitioners in determining the duration of intra-oral ulcer to consider urgent referral. Conclusion:Medical and dental practitioners showed areas of differences in practice, attitude and knowledge of oral and oropharyngeal cancer that when addressed would lead to improved survival rates.