The US Food and Drug Administration (FDA) published a proposed standard for N-nitrosonornicotine (NNN) content in finished smokeless tobacco (ST) products. The proposed NNN limit of 1 part per million dry weight (ppm dw) was derived based on a target excess lifetime cancer risk (ELCR), although the rule states the increased risk of oral cancer was the impetus for the rule. A review of the quantitative risk assessment (QRA) conducted by FDA was undertaken, with findings from this review indicating deficiencies in FDA’s QRA. First, the methods used to estimate the NNN cancer slope factor are inconsistent with derivation methods recommended by the US Environmental Protection Agency (EPA) and methods supported by FDA. Second, key input assumptions (i.e., body weight and lifespan) are inconsistent with current EPA recommendations in risk assessment practice. Third, the absorption factor estimated by FDA was incomplete. Fourth, the estimated ELCR in the proposed rule conveys an unrealistic level of precision, inconsistent with EPA recommendations. Finally, it is not clear that an ELCR calculation is relevant for the establishment of an NNN limit: ELCR is inadequate as a measure of excess cancer deaths in the population, because it does not account for competing mortality. However, if the ELCR is calculated in accordance with current EPA risk assessment guidance, an NNN level ≥5 ppm dw would result. This range is consistent with, or lower than, historical NNN levels in the ST products used by participants in Swedish epidemiological studies demonstrating no meaningful increase in oral cancer risk. There is no evidence that suggests setting the product standard to a ≥5-fold lower concentration of NNN will further reduce cancer risks in ST users.