Snus-induced lesions (SILs) are mucosal changes that are regularly seen in users of moist snuff (snus). Their role in oral carcinogenesis remains undefined. Our aim was to assess the natural course of SILs over several decades. A cohort of 1,115 individuals with SILs, confirmed in 1973-1974 during a population-based survey was followed for 27-29 years through multiple record linkages with virtually complete population- and health registers. A sample (n = 267) of the cohort members were invited for reexamination after 19-22 years. Register-based follow-up through January 2002 revealed a total of 3 incident cases of oral cancer (standardized incidence ratio of 2.3, 95% CI 0.5-6.7), none of which occurred at the site of the original SIL. There was a strong association noted between the degree of SIL and current snus consumption. The SILs had disappeared in all 62 individuals who had permanently quit using snus. In no case did we observe an important clinical change for the worse among individuals who had decreased their use or continued unabatedly. While the incidence of oral cancer in this cohort of individuals with SILs tended to be higher than expected, we conclude that cancers rarely occur at the site of lesions observed in the distant past.