Every year, over 50,000 women in the United States are diagnosed with the non-lethal form of breast cancer known as ductal carcinoma in situ (DCIS). When a diagnosis of DCIS is confirmed on biopsy, most women are treated with partial mastectomy and breast irradiation or elect total mastectomy as a means to avoid radiation therapy. Newer approaches to treatment for DCIS have suggested that surgical excision and observation, with or without endocrine therapy, may be an alternative for small volume, low grade DCIS. However, as a general rule, the underlying biology of DCIS is just beginning to be considered in the context of treating DCIS. A substantial body of basic science regarding the underlying molecular alterations present in DCIS suggests there are two major pathways of progression constituting an indolent and aggressive form of DCIS. The goal of this proposal Is to translate the research data on the numerous molecular genetic abnormalities present In DCIS into a pathology classification algorithm based on a restricted set of molecular, immunohistochemical, or morphologic features that will reliably Identify low grade and high grade progression pathways in DCIS. This would promote conservative treatment strategies for a subset of women with favorable prognosis DCIS and reduce the potential unfavorable consequences of over treating indolent breast disease.