Early-life exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or diets high in fat has been associated with an increased risk of cancer. La Merrill et al. (p. 596) investigated how developmental exposure to TCDD and a high-fat diet (HFD) might interact to alter breast cancer susceptibility in a laboratory animal model. Pregnant mice were exposed to TCDD or vehicle and were assigned to a low-fat diet or HFD at parturition. Female offspring were maintained on the same diets after weaning and exposed at various times to 7,12-dimethylbenz[a]anthracene to initiate mammary tumors. The authors report that maternal TCDD exposure doubled mammary tumor incidence in HFD-fed mice. Among HFD-fed mice, maternal TCDD exposure caused rapid mammary development with increased cytochrome P450 (Cyp1b1) gene expression and decreased catechol-O-methyltransferase gene expression. Cyp1b1 expression was also increased in mammary tumors following maternal TCDD exposure. The authors conclude that HFD may increase breast cancer in offspring with maternal TCDD exposure by altering estrogen metabolism. These results suggest a potential mechanism linking early-life TCDD exposure and HFD to breast cancer in humans.