The purpose of this study was to determine the outcome of breast cancer patients sustaining local-regional failure as their first site of relapse in an effort to group patients into prognostic categories. Between January 1970 and December 1992, over 4,000 patients with breast cancer were treated at our facilities with mastectomy or conservative surgery with radiation therapy (CS + RT). Two hundred thirteen patients sustained local-regional relapse without evidence of distant metastasis as their first site of failure, and they served as the population base for this study. The 213 patients with local-regional recurrence of disease were distributed as follows: 68 patients relapsed in the ipsilateral breast following CS + RT within 5 years of original diagnosis (EARLYBR). Fifty-one patients relapsed in the ipsilateral breast after 5 years from original diagnosis (LATEBR). Thirty-five patients relapsed in the chest wall within 5 years following mastectomy (EARLCW). Eighteen patients relapsed in the chest wall later than 5 years following mastectomy, and 41 patients failed in the regional lymphatics following mastectomy or CS + RT (REGREC). Patients with breast relapses were generally treated with salvage mastectomy, and patients with chest wall or regional nodal relapses were treated with radiation to the chest wall, regional nodes, or both. Systemic therapy at the time of local-regional relapse was highly individualized, ranging from observation to tamoxifen to high-dose chemotherapy with transplantation. With a median follow-up of 14 years, the overall 10-year survival for all 213 patients was 61%, and the 10-year distant metastasis-free rate was 59%. Patients with a LATEBR had a relatively favorable prognosis with a 5-year postrelapse distant metastasis rate of 80%. Patients with EARLYBR and LATECW had a similar prognosis, with a 5-year postrelapse distant metastasis rate of 61% and 65%, respectively. Patients with an EARLCW had a 5-year distant recurrence-free rate following a local relapse of 42%. Ten-year survivals from original diagnosis were 62% and 50%, respectively, and distant metastasis-free survival rates were 56% and 52%, respectively. Patients suffering REGREC following mastectomy or CS + RT carried a poor prognosis with a 10-year survival of 33% and a 10-year distant metastasis-free rate of 30%. Patients sustaining local-regional relapse as a first site of failure may be divided into prognostic groups. Patients with LATEBR have a relatively favorable prognosis. Patients with EARLYBR and CWREC have a poorer prognosis with a distant metastatic rate of approximately 50% within 5 years of local-regional relapse. Patients with REGREC have the poorest prognosis. Placing patients with breast cancer and local-regional relapse into these prognostic categories may be helpful in decision making regarding the role of systemic therapy at the time of local-regional relapse.