Developmental programs can be co-opted to drive cancer progression. Embryos are born with a set of genetic blueprints encoded in their DNA, yet during development, cells diversify to take on new fates above and beyond their genomes. This diversification is enacted in part by transcriptional/epigenetic programs as well as cell-cell interactions. Similarly, tumor cells utilize many of these same developmental programs but do so in the face of a highly disordered genome. Understanding how the cancer genome interacts with these developmental programs is central to determining which cells are capable of tumor initiation and how they metastasize. I will discuss our recent findings on how these developmental principles can be used to understand cancer initiation and progression.