The Interactive RadioEpidemiological Program (IREP) is a Web-based, interactive computer code that is used to estimate the probability that a given cancer in an individual was induced by given exposures to ionizing radiation. IREP was developed by a Working Group of the National Cancer Institute and Centers for Disease Control and Prevention, and was adopted and modified by the National Institute for Occupational Safety and Health (NIOSH) for use in adjudicating claims for compensation for cancer under the Energy Employees Occupational Illness Compensation Program Act of 2000. In this paper, the quantity calculated in IREP is referred to as “probability of causation/assigned share” (PC/AS). PC/AS for a given cancer in an individual is calculated on the basis of an estimate of the excess relative risk (ERR) associated with given radiation exposures and the relationship PC/AS = ERR/ERR+1. IREP accounts for uncertainties in calculating probability distributions of ERR and PC/AS. An accounting of uncertainty is necessary when decisions about granting claims for compensation for cancer are made on the basis of an estimate of the upper 99% credibility limit of PC/AS to give claimants the “benefit of the doubt.” This paper discusses models and methods incorporated in IREP to estimate ERR and PC/AS. Approaches to accounting for uncertainty are emphasized, and limitations of IREP are discussed. Although IREP is intended to provide unbiased estimates of ERR and PC/AS and their uncertainties to represent the current state of knowledge, there are situations described in this paper in which NIOSH, as a matter of policy, makes assumptions that give a higher estimate of the upper 99% credibility limit of PC/AS than other plausible alternatives and, thus, are more favorable to claimants.