Background: Over 300 genetic variants contribute to overall risk; however, the functional polymorphisms remain elusive. Even for high-risk variants in BRCA1 and BRCA2, penetrance is significantly influenced by family history, indicating the presence of genetic modifiers. Cell-based models of breast epithelium representing the genetic diversity among women are needed to elucidate the complex genetic interactions and mechanisms that can be harnessed to predict risk and provide individualized prevention strategies. Therefore, we compared the requirements for establishing stable cell lines using normal breast cells from diverse donors differing in breast cancer risk. Results: Normal breast epithelial cells were obtained from 17 donors that included individuals carrying germline mutations in BRCA1, BRCA2 and TP53 (high risk) as well as individuals without a familial history of breast cancer (average risk). Co-expression of CDK4 and TERT yielded cell lines from 100% of donors compared to only 30% using TERT alone. The immortalized cells retain p53 function and become senescent when CDK4 is inhibited. The methods preserve populations of cells expressing both luminal and basal cell markers, with a subset retaining expression of estrogen receptor alpha (ESR1) and functional estrogen signaling. Further characterization of a subset of cell lines demonstrates luminal progenitor cell features and their ability to form polarized acini when grown as 3D cultures in extracellular matrix. Conclusions: Combined expression of CDK4+TERT provides a robust method to consistently obtain immortalized breast cells from genetically diverse donors. These cells retain characteristics of both luminal and basal epithelial cells, providing in vitro tools for investigating key aspects of human breast cancer pathogenesis, including the transition from normal to breast cancer cells, hormonal responses, and the genetic mechanisms underlying fidelity of DNA replication and repair.