Malignant transformation of an epithelium occurs within the context of a dynamically evolving tissue stroma that is composed of multiple cell types surrounded by an extracellular matrix. Because stromal-epithelial interactions regulate tissue homeostasis and can profoundly influence tumorigenesis it has been proposed that the stromal microenvironment is an epigenetic tumor modifier that can either positively or negatively regulate the malignant behavior of genetically aberrant cells. New work reported in this issue of Journal of Cell Science now provides compelling evidence that alterations in the stroma are necessary and also sufficient for induction of malignant behavior by genetically normal cells.