MCF10DCIS.com cells form comedo type ductal carcinoma in situ in immune‐deficient mice before forming invasive ductal carcinoma. As the lesions mature, both stromal and epithelial cells undergo phenotypic changes detected by immunohistochemistry. Myofibroblasts are present before the formation of carcinoma in situ and after development of invasive carcinoma. MCF10DCIS. com lesions develop a myoepithelial layer prior to exhibiting a basement membrane surrounding the ductal mass. TGFβ1 is initially expressed by the epithelial cells but is expressed by stroma in invasive carcinoma. Stromal derived factor‐1 is detected in epithelial cells in early carcinoma in situ but is produced in stromal cells in invasive carcinoma. The receptor CXCR4 is expressed by epithelial cells in the xenografts at all times, as is the hepatocyte growth factor receptor c‐met. MCF10DCIS.com xenografts illustrate the dynamic interplay of epithelium and stroma in the development of carcinoma in situ and subsequent invasive carcinoma. Although the phenotype of the epithelial cells may be dependent upon the stroma, the malignant epithelium induces the development of the stroma necessary for progression to the invasive stage. © 2007 Wiley‐Liss, Inc.