Abstract: A three-dimensional in vitro culture system comprising breast epithelial cells, endothelial cells and breast fibroblasts supports growth and functional differentiation of preneoplastic breast epithelial cells and endothelial cells and recapitulates estrogen induced in vivo effects on angiogenesis and proliferative potential of breast epithelial tissue. This model permits the generation of functional vascular networks and local proliferative ductal alveolar outgrowths with invasive potential. Both these processes are augmented by estrogen. This culture model is used to evaluate agents for their effects, whether stimulatory or inhibitory, on preneoplastic breast disease and its progression to cancer.