Oral cancer, ranking sixth in the cancer incidence worldwide, is one of the most common neoplasms. Preneoplastic or premalignant (precancerous) lesions are lesions that can potentially transform into malignancy in a variety of tissues, including the oral cavity. Such oral lesions may be caused by tobacco use, exposure to the human papillomavirus and chewing of the betel nut. These substances contain carcinogens and/or tumor promoters. The mucosa of the oral cavity is covered with squamous epithelium and is relatively resistant to injury. However, exposure to these substances can cause the mucosa to undergo changes. The changes are usually initiated by a leukoplakic patch. While some leukoplakic patches recover and resolve, others progress to squamous cell carcinoma with or without invasion. Other premalignant lesions include oral submucous fibrosis, which is a potentially malignant condition caused by the abuse of the betel nut. Understanding the histology, premalignant states and molecular mechanisms of oral carcinogenesis may facilitate the development of novel strategies for the prevention and treatment of oral cancer. In addition, early detection is of critical importance to improve the survival rates of patients with oral cancer. In this review, we will summarize these aspects of oral cancer development, beginning from the histology of the oral cavity.