Gene expression profiling was performed on laser captured breast stroma and epithelium obtained from 14 breast cancer patients. As with breast epithelium, of the stromal gene expression changes observed between normal tissue and invasive ductal carcinoma, greater than 90% occurred early, at the normal to ductal carcinoma in situ transition. Only 10% of stromal and 0% of epithelial genes were differentially regulated between non-invasive ductal carcinoma in situ and invasive disease. These data suggest that the majority of gene expression changes required for transformation occur early, prior to histological evidence of an invasive phenotype, the stroma cooperates closely with epithelium in this transformation, and for acquisition of the invasive phenotype, the stroma is dominant over the epithelium.