Although approximately 50,000 cases of axillary node-negative breast cancer are diagnosed in the United States annually, the natural history of this heterogeneous disease is incompletely defined. Several series have reported 5-year relapse-free and overall survival ranging from 56% to 89% and 74% to 92%, respectively. Tumor necrosis and anaplastic morphology correlate with early treatment failure. The estrogen receptor and size of the primary tumor are probably also predictive of clinical course. Thus far, perioperative cyclophosphamide is the only systemic treatment demonstrated to prolong survival in a statistically significant fashion. Several ongoing studies are investigating the role of tamoxifen or cytotoxic chemotherapy, or both, in prospective randomized trials. However, too few patients with insufficient follow-up have been analyzed to permit definitive conclusions or recommendations.