While carcinogenicity of smokeless tobacco (ST) to humans is well established the oral lesions that precede development of cancer are less well characterized. The clinical appearances of ST-associated lesions are variable. Epidemiological studies show a strong significant association of risk with chronic daily use but population differences are noted because of various commercial products in use. Morphological features observed are some what different to oral lesions caused by smoking and oral dysplasia in ST-associated lesions is less common. Effects of ST on oral keratinocytes observed in vitro include alterations in cell proliferation, apoptosis and activation of inflammatory markers. Genetic aberrations caused by ST include activation of ras, uncommon in smokers but mutational hot spots in p53 encountered are similar to those in smokers.