In order to understand why breast cancer develops as well as predict the outcome of pharmacological treatments, we need to model the structure and function of organs in culture so that our experimental manipulations occur under physiological contexts. In the presence of the correct signaling from growth factor and extra-cellular matrix proteins, human breast epithelial (HBE) cells form their original phenotype in vivo. HBE cells in the absence of reconstituted basement membrane extract (rBME) fail to assemble organized structures, and arrest growth when they reached confluence. HBE cells embedded inside or on the top of rBME could display an acinar structure with a dead luminal space in the absence of epidermal growth factors (EGF). This emulated the ductal structures breast epithelial cells found in vivo. Under the same condition, carcinoma cells exhibited severe morphological deformities, including colony overgrowth, luminal filling, and resistance to apoptosis. It was observed that EGF disrupted the formation of luminal structures of HBE either in monolayer or in 3 dimensional culture with rBME. When EGF was reduced or removed, normal phenotypes (e.g. luminal structure and uniformed size) of human breast epithelial cell was achieved.