Within the past year, the draft sequence of the human genome was completed and made available to researchers worldwide. Recent advances in technology along with the vast amount of sequence data on the human genome now provide a previously unimagined means of defining the genetic architecture of cancer cells. Implicit in this approach is the ability to describe the evolution of that architecture as normal breast cells progress toward the malignant phenotype. Ongoing experiments involving the simultaneous analysis of the entire genome in a high-throughput manner are expected to reveal those genes and regulatory mechanisms that are critical at each step of progression toward malignancy, including (1) providing a growth advantage over normal cells, (2) maintaining the malignant state, (3) modulating response to therapy, and (4) developing metastatic potential. Once these data are available, the ability to design preventive, diagnostic, prognostic, and therapeutic tools directed at those targets will be within reach.