Because three is usually more extensive toxicity, metabolism, and pharmacokinetic information for pharmaceuticals as opposed to environmental agents, including pesticides, the argument has been made that carcinogenicity testing in two rodent species may not have been necessary for carcinogenicity testing of pharmaceuticals. On the basis of numerical data only, it may be argued that carcinogenicity testing of pharmaceuticals in one species, typically the rat, is sufficient to identify potential human carcinogens. The argument that testing in a second species, typically the mouse, is redundant overlooks the value added by the second species carcinogenicity study. Bioassay data from the second species allows balance and perspective in evaluating the observed effects, and this is especially critical when there is a marginal, questionable, or inconclusive response in one species. Utilization of two species for carcinogen identification is the principal means for identifying trans-species carcinogens-those mostly likely to be carcinogenic in humans. Given that neither rat nor mouse are ideal surrogates for humans, concordant data from both species strengthens the ability to extrapolate findings to humans. We believe that testing in two species should continue to be the default approach used for carcinogen hazard identification whenever scientifically indicated until such time that acceptable and suitable alternatives are available. To utilize only one species for this important means of protecting human health is premature at this time.