A 67-year-old advanced breast cancer patient with multiple bone metastases showed a remarkable response to the combination therapy of mitoxantrone (MIT) and medroxyprogesteron acetate (MPA) after failure of anthracycline therapy. Eight course of CTF (cyclophosphamide, THP-adriamycin, 5-fluorouracil) and subsequent 4'-epi-adriamycin were performed for locally advanced breast cancer and multiple bone metastases, but the ulcerated breast cancer enlarged. Then the combination therapy of MIT (10 mg/day) and MPA (1,200 mg/day) was carried out. Seven months after treatment, the ulcerated breast cancer disappeared completely and the serum levels of CA 15-3, TPA and CEA decreased within the normal range. These results suggest that combination therapy with mitoxantrone may well be effective against the anthracycline-resistant breast cancer.