BACKGROUND: To determine whether, when primary breast cancer is treated by local excision supported by systemic therapy appropriate to the oestrogen receptor status (ER) of the tumour, local radiotherapy can be avoided. METHODS: We carried out a randomised controlled trial in 585 patients aged less than 70 years with primary breast cancers of 4 cm or less in size in four specialist units and seven other hospitals in Scotland. After local excision of the tumour (1 cm margin) and an axillary lymph-node clearance or sample, all patients received systemic therapy with oral tamoxifen 20 mg daily or six 3-weekly intravenous bolus injections of cyclophosphamide 600 mg, methotrexate 50 mg, and fluorouracil 600 mg per m2, depending upon the ER concentration in the primary tumour. Patients were then randomly allocated to postoperative radical radiotherapy (50 Gy to breast with boost to the tumour bed) or to no further local treatment. The median follow-up of living patients was 5.7 years. The primary analysis was by intention to treat but since some patients did not receive systemic therapy appropriate to their ER status, a subsidiary analysis was restricted to 464 patients in whom all details of the protocol had been observed. FINDINGS: In the primary analysis survival was equal in the radiotherapy and non-radiotherapy groups (hazard ratio [HR] 0.98, 95% CI 0.67-1.44). Event-free survival showed an advantage in the irradiated patients (HR 0.54, 95% CI 0.39-0.74), largely due to fewer loco-regional relapses (HR 0.20, 95% CI 0.12-0.33). The relapse rate in the ipsilateral breast was 24.5% in the non-irradiated group and 5.8% following breast irradiation. The subsidiary analysis confirmed these findings and indicated the advantage of radiotherapy irrespective of ER concentration. There was a non-significant trend towards fewer distant metastases in the irradiated group. INTERPRETATION: After local excision of a primary breast cancer, we conclude that radiotherapy to the residual breast tissue is advisable even when selective adjuvant systemic therapy is given.