Twenty-two patients with advanced breast cancer have been treated with sequential chemo-hormonotherapy consisting of tamoxifen 20 mg/day orally for 14 consecutive days, followed by no therapy for ten days, then estrogen 0.625 mg/day orally for three days; the next day methotrexate 200 mg/m2 i.v. and cyclophosphamide 600 mg/m2 i.v.; after 24 hours folinic acid 200 mg/m2 i.v. and 5-fluorouracil 600 mg/m2 i.v. Fifteen patients were evaluable for response, 22 were evaluable for toxicity. All but one were heavily pretreated with chemo and/or hormonotherapy. Nine of 15 had previously received palliative CMF (cyclophosphamide, methotrexate, 5-fluorouracil) (mean 9 cycles), and one patient 12 cycles adjuvant CMF. Thirteen of 15 previously received tamoxifen (median treatment of 18 months). Six patients had multiple metastatic disease, while five had visceral involvement. They were all postmenopausal, with median age 57 years, and median disease-free interval 31 months. ER status was not known and the median ECOG performance status was 1. Overall response rate was 20%. Only one patient attained complete remission; 46.6% were stable disease and 33.3% progressive disease. Accepting that the response rate is very low in pretreated patients, this 20% can be significant. Ninety cycles were administered to 22 patients and the treatment was very well tolerated: both hematologic and nonhematologic toxicities were mild.