Two hundred fifty-seven patients with oral leukoplakia were studied and followed for an average period of 7.2 years. All lesions were more than one cm in size and had been present and observed for a minimum of 6 months. Of the initial biopsies, 235 revealed a benign hyperkeratosis and 22 others contained some degree of epithelial dysplasia. Seventy-three percent of the patients used tobacco, with cigarette usage being the predominant form. Forty-five patients (17.5%) subsequently developed squamous carcinomas in the hyperkeratotic epithelial site in an average time of 8.1 years. Eight of these malignant transformations came from patients who originally had epithelial dysplasia. High risks for malignant transformation also included non-smoking patients, the clinical presence of erythroplasia (erythroleukoplakia), and a clinical verrucous-papillary hyperkeratotic pattern. Duration of the leukoplakia progressively increased the total number of malignant transformations, with the largest rate occurring in the second year. This study confirms that oral leukoplakia is a precancerous lesion and that certain characteristics indicate greater risks and warrant consideration of more aggressive management.