Purpose: To analyse the therapeutic effect and toxicity of re-irradiation (re-RT) combined with hyperthermia (HT) following resection or clinically complete remission (CR) of persistent locoregional recurrent breast cancer in previously irradiated area. Methods and materials: Between 1988 and 2001, 78 patients with high risk recurrent breast cancer underwent elective re-RT and HT. All patients received extensive previous treatments, including surgery and high-dose irradiation (≥50Gy). Most had received one or more lines of systemic therapy; 44% had been treated for ≥ one previous locoregional recurrences. At start of re-RT+HT there was no macroscopically detectable tumour following surgery (96%) or chemotherapy (CT). Re-RT typically consisted of eight fractions of 4Gy, given twice weekly. Hyperthermia was added once a week. Results: After a median follow up of 64.2 months, three-year survival was 66%. Three- and five-year local control rates were 78% and 65%. Acute grade 3 toxicity occurred in 32% of patients. The risk of late ≥ grade 3 toxicity was 40 after three years. Time interval to the current recurrence was found to be most predictive for local control in univariate and multivariate analysis. The extensiveness of current surgery was the most relevant treatment related factor associated with toxicity. Conclusions: For patients experiencing local recurrence in a previously radiated area, re-irradiation plus hyperthermia following minimisation of tumour burden leads to a high rate of local control, albeit with significant toxicity. The latter might be reduced by a more fractionated re-RT schedule. © 2010 Informa UK Ltd All rights reserved.