Cancers of the oral cavity, oropharynx, lip, and salivary glands are malignancies of the head and neck. Some of these cancer sites share risk factors, although each has distinctive anatomic, epidemiologic, and clinical features. Oral cavity cancers arise on the inner lip and buccal mucosa, anterior two-thirds of the tongue, gum, hard palate, and floor of mouth. These cancers are strongly associated with the use of smoked and smokeless tobacco products, heavy alcohol consumption, and chewing of betel quid or pan, but only minimally associated with prior infection with human papillomavirus (HPV). In contrast, oropharyngeal cancers affect the posterior one-third (base) of the tongue, tonsils, soft palate, and other oropharyngeal tissues and are strongly associated with HPV-16 infection as well as with the use of tobacco, alcohol, and betel quid. In principle, tumors of the oral cavity, oropharynx, and lip are among the most preventable forms of cancer.