Dysplastic and hyperplastic proliferative lesions with graded severity of atypia are recognized in a number of tissues and are generally suspected to be premalignant, that is to say at high risk for further progressing to carcinoma in situ and invasive cancer. However, few xenograft models of premalignancy for any organ site have been successfully developed. A good model of human premalignant breast disease would lead to lesions which resemble high risk human breast disease in xenografts and sporadically progress to invasive cancer with time. In this chapter the use of breast tissue pieces and epithelial cells for establishment of xenografts and the development of human breast epithelial cell lines that form premalignant xenograft lesions are described. MCF10AT cells not only form simple differentiated ducts which persist in xenografts and sporadically progress to carcinoma, but also form intermediate proliferative lesions resembling proliferative disease without atypia, atypical hyperplasia, and carcinoma in situ.