The U.S. Food and Drug Administration (FDA) has advanced a proposed product standard of 1 µg/g N-nitrosonornicotine (NNN) content in finished smokeless tobacco (ST) products, citing selected findings from epidemiology to support the proposed limit. The purpose of this work was to evaluate FDA’s application of epidemiological literature. An independent review was undertaken, and identified a number of inaccuracies. First, FDA combines oral cancer relative risk (RR) estimates for men and women, which is inappropriate given the RR between genders are widely different. Furthermore, men are the predominant users of ST. Second, FDA relied upon Swedish epidemiology to indicate current (low) levels of NNN in modern Swedish ST products are not associated with increased risk of oral cancer; however, NNN levels in Swedish ST in use during the time of the epidemiology studies were higher than levels in current products. Third, FDA relied on studies of international ST products (e.g. Asia and Africa), yet the composition and use behaviors associated with ST products unique to Asia and Africa differ markedly from those of U.S. products, and are not relevant to US ST products and users. Fourth, NNN concentrations in products used by study participants in the available epidemiology studies cannot be estimated precisely, and there is substantial heterogeneity in the concentration of NNN and other toxicants across and within ST product types. Finally, FDA’s conclusion that NNN is the predominant driver of excess oral cancer risk among ST users is inconsistent with existing scientific data, as urinary levels of NNN are generally higher among ST users compared with smokers, yet smokers incur a substantially higher risk for oral cancer than ST users. Thus, considered objectively, the available epidemiology data do not support the proposed NNN standard.