Extensive research has been conducted over several decades understanding the genetic changes that occur in normal cells to promote them towards a transformed state. However, it is becoming increasingly apparent that carcinoma growth requires more complex interactions for development and progression. Since tissue epithelium is composed of highly specialized cells that orchestrate specific activities, their proper development and function is highly dependent on contextual signals from the stroma. As such, it is conceivable that carcinoma development should also parallel these needs. In light of our recent evidence combined with established work demonstrating the role of the tissue stromal environment in cancer development, it is evident that tissue stroma exhibits context specific tumor suppressive and tumor-promoting abilities that serve to regulate dysfunction and neoplastic growth of the epithelium.