In animal and laboratory models, cancer-associated stroma, or elements of the supporting tissue surrounding a primary tumor, has been shown to be necessary for tumor evolution and progression. However, little is understood or studied regarding the properties of intact stroma in human cancer in vivo. In addition, for breast cancer patients, the optimal volume of local tissue to treat surrounding a primary tumor is not clear. Here, we performed an interdisciplinary study of normal-appearing breast tissue using breast magnetic resonance imaging (MRI), correlative histology and array comparative genomic hybridization to identify a cancer-associated stroma in humans. Using a novel technique for segmenting breast fibroglandular tissue, quantifiable topographic percent enhancement mapping of the stroma surrounding invasive breast cancer was found to be significantly elevated within 2 cm of the tumor edge. This region was also found to harbor increased microvessel density, and genomic changes that were closely associated with host normal breast tissue. These findings indicate that a cancer-associated stroma may be identified and characterized in human breast cancer using non-invasive imaging techniques. Identification of a cancer-associated stroma may be further developed to help guide local therapy to reduce recurrence and morbidity in breast cancer patients.