This perspective on Murillo et al. (beginning on page 942 in this issue of the journal) examines the potential of the naturally derived agent deguelin to prevent mammary tumorigenesis. These investigators showed that deguelin inhibits wnt/beta-catenin signaling in breast cancer cell lines, in addition to inhibiting other previously reported signaling pathways. Our growing understanding of deguelin mechanisms could lead to important advances in the prevention of estrogen receptor-negative breast and other cancers.