A total of 56 heavily pretreated patients with advanced breast cancer were treated with the combination mitomycin and mitoxantrone. Partial responses were seen in ten of 56 patients (18%), or ten of 44 (23%) completing two courses, while 18 (32%) had stable disease. Responses were seen in eight patients failing doxorubicin. The median duration of response was 26 weeks, with responders surviving a median of 37 weeks. A total of 59% of the courses were associated with World Health Organization grade 3 or 4 neutropenia (less than 1.0 X 10(9) cells/L). Nausea and vomiting were minimal. Mitomycin and mitoxantrone has activity in heavily pretreated patients with advanced breast cancer.