OBJECTIVE The aim of the present study was to determine the prevalence and the relationship of oral mucosal lesions in tobacco users and denture wearers in a North Indian population. METHODS The study comprised 3,749 patients attending the Department of Oral Medicine and Radiology, Jodhpur Dental College General Hospital between September 2008 and December 2012, for the treatment of dental problems other than oral mucosal lesions. The ages ranged from 28 years to 83 years, with a mean age of 49.7 years. The results were evaluated using the Pearson Chi-square test, with Yate's correction and ANOVA tests. RESULTS A total of 2,318 patients were diagnosed with lesions associated with the use tobacco and the wearing of dentures. The most frequently seen lesion was melanin pigmentation (29.9%) followed by linea alba (22.2%) and frictional keratosis (19.9%). Ulcers (6.1%) were the most common oral lesion seen in patients who wore dentures, followed by hyperplasia (4.8%). A statistically significant relation (P < 0.05) was established between tobacco and melanin pigmentation, frictional keratosis, traumatic ulcerations and leukoplakia. In those who wore dentures a statistically significant relation (P < 0.05) was found between candidiasis, traumatic ulceration and frictional keratosis. CONCLUSIONS The results of the present study indicate that the association of frictional keratosis with tobacco users and wearers of dentures can help in determining the diagnosis and treatment plan for oral cancer. Wearers of dentures should also be recalled for periodic checks at regular intervals and optimum preventive measures implemented.