Background: Although the conservation management of breast cancer has become a routine method of treatment in most centers, there is still considerable controversy surrounding the ultimate minimum treatment required for node-negative breast cancer to achieve adequate local control. Purpose: Our purpose was to assess the value of breast irradiation in reducing breast relapse following conservation surgery for node-negative breast cancer. We attempted to define low-risk groups of women for breast and distant site relapse (i.e., recurrence outside the breast) who might be spared breast irradiation or adjuvant systemic therapy. Methods: Eight hundred thirty-seven patients were randomly assigned to receive radiation therapy or no radiation therapy following lumpectomy and axillary dissection for node-negative breast cancer. Results: Breast irradiation reduced relapse in the breast from 25.7% in the controls to 5.5% in the irradiated patients. There was no difference in survival between the two groups (median follow-up, 43 months). A low-risk group (<5%chance of relapse in the breast without irradiation) could not be defined. Tumor size (>2 cm), age (<40 years), and poor nuclear grade were important predictors for breast relapse. Age (<50 years) and poor nuclear grade were important predictors for mortality. The presence of ductal carcinoma in situ did not predict breast relapse. Conclusions: Breast irradiation significantly reduces breast relapse, but it does not influence survival. Important predictors of breast relapse are age, tumour size, and nuclear grade predict survival. Implications: Further follow-up may define an acceptable low-risk gropu for breast relapse. Until then, we recommend that all patients receive breast irradiation. Systemic adjuvant theraphy should be considered for patients with poor nuclear gradetumors. [J Natl Cancer inst 84:683–689, 1992]