This study analyzed prognostic factors at primary diagnosis and at first recurrence for impact on survival after isolated locoregional failure. The aims were: (1) assessment of prognostic factors for time to second locoregional failure, distant failure, and survival in isolated locoregional recurrence of breast cancer after mastectomy; and (2) investigation of the impact of a second locoregional failure on dissemination and survival.Between 1983 and 1985, 99 patients who had undergone mastectomy and then developed isolated local and/or regional recurrences, were treated with radical excision and radiotherapy; none of these patients had distant metastases. Survival and the times to second local failure and distant metastasis were analyzed according to potential prognostic factors.The median follow-up was 123 months; 38 patients were still alive. Median survival was 89 months and the 10-year survival rate was 38%, with no difference between local and regional recurrences. A total of 43 patients developed a second locoregional recurrence after a median of 73 months; primary tumour size and initial node status were significant independent prognostic factors. The annual hazard rates for recurrence were similar for patients developing local failure or systemic recurrence. The 10-year rate of dissemination was 49% for patients with locoregional control, compared with 51% for patients who had a second locoregional recurrence. The prognostic factors for survival were node status at mastectomy and haemoglobin level at first recurrence.The development of a second locoregional recurrence was not associated with an increased risk of dissemination or reduced survival. Differences in prognostic factors for locoregional control and distant metastases suggest that these recurrences represent different biological entities that require different treatment strategies. However, as the achievement of locoregional control had no influence on prognosis, the use of systemic adjuvant therapy may be warranted in a subset of these patients.