The importance of stromal cells and the factors that they express during cancer initiation and progression has been highlighted by recent literature. The cellular components of the stroma of epithelial tissues are well-recognized as having a supportive role in carcinogenesis, where the initiating mutations of a tumor originate in the epithelial cells. The use of mouse models and xenografts suggests that mutations in the stromal fibroblasts can also initiate epithelial tumors. Many of these tumors result from the alteration of paracrine growth factor pathways that act on the epithelia. However, the tissue specificity of the responses to the growth factors is a mystery not yet solved.