Smokeless tobacco, particularly snuff, is a recognized risk factor for cancer of the oral cavity. This conclusion rests in large part on epidemiologic studies of oral cancer in women, especially in the American South, where the oral cancer death rate in females has been high. The research focus on studies of women led to the identification of the hazards from smokeless tobacco use; the strategies used are broadly applicable to studies of the etiology of other cancers in both women and men. High levels of nitrosamines, which are potent carcinogens, are found in smokeless tobacco products. Steps should be taken to reverse the alarming increase in their use by men and boys. More research attention also should be directed to understanding new emerging trends in oral cancer mortality among women.