The US Food and Drug Administration (FDA) draft guidance for industry (2012) provides abbreviated lists of harmful and potentially harmful constituents (HPHCs) found in tobacco and cigarette smoke. As FDA considers the abbreviated HPHC list to be representative of the classes of hazardous compounds present in tobacco products or tobacco smoke, it can serve as the basis of a relative “whole-product” toxicological risk comparison for tobacco products (e.g., New Product to Predicate Product). A range of validated analytical techniques exist for quantification of individual HPHCs, which are reported as a mean value with a standard deviation. The objective of this presentation is to propose a method for incorporating analytical variance into a comparative quantitative risk assessment (QRA) framework to provide a more robust representation of relative toxicological risk between whole tobacco products. Using a cigarette example, we provide a general overview of the QRA framework (i.e., hazard assessment, exposure assessment, and risk characterization) and highlight how incorporating the analytical variance in HPHC yields into the exposure assessment and hazard characterization produces an estimate of the range of probable risk as opposed to a single (deterministic) point estimate. The range of risk for each individual HPHC is calculated for both cancer (i.e., Excess Lifetime Cancer Risk – ELCR) and non-cancer (i.e., Hazard Index – HI) effects, and these individual risk estimates are then aggregated into representative estimates of whole-product risk. Additionally, statistical analysis can be performed to assess whether there is a significant difference (p < 0.05) in risk between the products.