Determining how findings of chemically induced carcinogenic effects in rodents can properly be interpreted for human health poses a continuing challenge to the risk assessment community. One approach begins by comparing and contrasting carcinogenic process in rodents and humans, identifying biologically significant similarities and differences and gaps in scientific knowledge and understanding. Russo and Russo (in this issue) use just such an approach to evaluate the current state of scientific understanding of the comparative mechanisms of mammary tumorigenesis in humans and rodents, particularly the role of reproductive hormones. This commentary describes the basis for this review and suggests some of the implications the report may have for human health risk assessment and for future research.