Abstract For over a century the somatic gene mutation theory of cancer has been a scientific orthodoxy. Recent failures of causal explanations using this theory and lack of significant progress in addressing the cancer problem medically have led to a new competition of ideas about just what cancer is. This essay presents an alternative view of cancer as a developmental process gone wrong. More particularly, cancer is a break down in the autopoietic process of organ maintenance and the multi-cellular coordination of tissues. Breast cancer is viewed through a systems science perspective as an example of the importance of framing one’s theoretical assumptions before making empirical judgments. Finally, new understanding of the histoarchitecture of the interstitium is presented as a first principle of cancer: a process of cells coming from cells, invading the space between cells.