High-dose etoposide (1,500-2,500 mg/m2) was used for the treatment of 23 previously treated patients with advanced breast cancer. Six of 23 (26%) showed objective regression with a median duration of response of 5 months. Responses were seen at all sites apart from bone. Response was related to dose level with 11/23 responses of measurable lesions occurring at doses ≥ 2,000 mg/m2 as compared to 2/23 responses at a dose of 1,500 mg/m2. The treatment regimen was able to be given on an outpatient basis with only routine supportive measures. High-dose etoposide may come to play a role in high-dose combination chemotherapy regimens for advanced breast cancer.