Breast cancer is the most common cancer in American women and is second only to lung cancer as the leading cause of death among women with solid tumors. Although chemotherapy and hormonal therapy are widely used in the primary treatment of breast cancer, appropriate selection of patients for such treatment remains challenging. Traditional prognostic factors --such as age, lymph node status, tumor size, tumor grade, and hormone receptor status--have been useful in assessing the risk for development of metastatic disease and these have been incorporated into a program that is available online for risk assessment (www.adjuvantonline.com). Molecular markers have not been incorporated into this schema but certainly have the potential for further refining risk assessment. Once the risk of recurrence is established for each patient, this can then be used to determine the potential effectiveness of hormonal therapy, chemotherapy, or the combination of these treatments. While the use of this web-based system has certainly empowered physicians and patients in making adjuvant therapy decisions, it is inadequate for precise stratification of patient cohorts into responders versus non-responders to systemic agents. Identification of accurate prognostic indicators and predictors of response have the potential to profoundly impact treatment selection for individual patients. Further, identification of prognostic factors with underlying biology that can serve as therapeutic targets will be important for identification and treatment of high-risk patients. Here we discuss the role of cyclin E as a prognostic marker and predictive factor in breast cancer management and the potential to use this marker as a target for therapy.