This article presents a general model for estimating population heterogeneity and "lack of knowledge" uncertainty in methylmercury (MeHg) exposure assessments using two-dimensional Monte Carlo analysis. Using data from fish-consuming populations in Bangladesh, Brazil, Sweden, and the United Kingdom, predictive model estimates of dietary MeHg exposures were compared against those derived from biomarkers (i.e., [Hg]hair and [Hg]blood). By disaggregating parameter uncertainty into components (i.e., population heterogeneity, measurement error, recall error, and sampling error) estimates were obtained of the contribution of each component to the overall uncertainty. Steady-state diet:hair and diet:blood MeHg exposure ratios were estimated for each population and were used to develop distributions useful for conducting biomarker-based probabilistic assessments of MeHg exposure. The 5th and 95th percentile modeled MeHg exposure estimates around mean population exposure from each of the four study populations are presented to demonstrate lack of knowledge uncertainty about a best estimate for a true mean. Results from a U.K. study population showed that a predictive dietary model resulted in a 74% lower lack of knowledge uncertainty around a central mean estimate relative to a hair biomarker model, and also in a 31% lower lack of knowledge uncertainty around central mean estimate relative to a blood biomarker model. Similar results were obtained for the Brazil and Bangladesh populations. Such analyses, used here to evaluate alternative models of dietary MeHg exposure, can be used to refine exposure instruments, improve information used in site management and remediation decision making, and identify sources of uncertainty in risk estimates.