PURPOSE: To evaluate the tolerance of concomitant administration of anthracycline-based chemotherapy (CHT) and 3-dimensional conformal radiotherapy (RT) after breast-conserving surgery. METHODS AND MATERIALS: Sixty-seven patients, treated with conservative surgery followed by 3-dimensional whole breast RT and concomitant CHT regimens including “Canadian modified” CEF (5-fluorouracil, epirubicin, cyclophosphamide) or AC (doxorubicin, cyclophosphamide) were evaluated for toxicity. They were compared in terms in compliance and acute toxicity with 67 patients irradiated sequentially after having received anthracyclines. RESULTS: Acute grade ≥2 skin toxicity was significantly higher in the concomitant group compared to the sequential group, although the incidence of Grade 3 desquamation showed no statistical difference (9% vs. 3%, p = 0.14). Haematological toxicity represented the main cause of treatment discontinuation, reporting higher rate of grade 3-4 leuco-neutropenia in the concomitant group (20.9% vs. 6%, p = 0.01). Mean RT duration was longer in the concomitant group (51 days vs. 45 days) owing to RT breaks. Late toxicity was acceptable. No symptomatic lung and heart events were reported. Radiological lung hyperdensity was detected in 27.7% of the patients in the concomitant group. Post-treatment left ventricular ejection fraction significantly decreased compared with baseline, but cardiac function remained within the normal range, without any difference between left or right-sided RT. CONCLUSIONS: Although there was more acute grade ≥2 skin toxicity in the concomitant group, the rate of grade 3 dermatitis was lower than expected, suggesting some advantages of 3-D CRT over older techniques. Haematological toxicity exerted a significant impact on both RT and CHT delivery.