Objective To determine how information on chemical constituents of different smokeless tobacco products (STPs) may be used in cancer risk assessment for regulatory purposes. Methods This study investigated select STP constituents potentially associated with significant cancer risk by applying a known toxicological risk assessment framework. Cancer risk estimates were obtained for selected constituents of STPs and a medicinal nicotine gum formulation with comparable toxicity information and also median concentration data on the GothiaTek analytes. The calculated cancer risk was considered 'unacceptable' if it exceeded the US Environmental Protection Agency's (USEPA's) benchmark of an 'acceptable' cancer risk of 10E-6. Results The cancer risk estimates derived from daily use of 10 g of STPs meeting the industry-set GothiaTek limits exceed the levels generally considered 'acceptable' by the USEPA at least 8000 times. Except for the medicinal nicotine tested, all the STP types, including the relatively lower tobacco specific nitrosamine (TSNA)-containing snus, were found to carry an 'unacceptable' cancer risk. The calculated cancer risks associated with the snus and the US moist snuff products were, respectively, at least 1000 times and 6000 times greater than the minimum acceptable. TSNA and cadmium are associated with the largest estimated cancer risks for all the STPs evaluated. Conclusions This study's findings provide an empirical risk assessment that could guide STP regulation using an existing toxicological assessment framework. The study findings question the scientific rationale of the industry-set standards and highlight the need for regulatory actions to reduce specific toxicants in all STPs.