Abstract:Sensitive assays that recapitulate the complex and dynamic interaction of cells within the breast are needed to understand the early steps by which normal breast cells become cancerous, and cancer cells become invasive. We discuss the literature of available culture systems and elaborate on two assays we have developed to study interaction of normal and tumor cells with stromal cells and ECM in three dimensions. The assays highlight the significance of cell:cell and cell‐extracellular matrix interactions in functional differentiation of the breast epithelium and should provide valuable tools in understanding breast cance