Etoposide has played a prominent role in the treatment of many common and uncommon malignancies. The use of etoposide in the treatment of breast cancer is still experimental. Early work using etoposide as a single agent in previously treated patients suggests this drug is inactive in the dose and schedules tested. The sole trial using etoposide as a single agent in untreated patients suggests a modest overall response rate of 15%. Perhaps more promising has been the use of etoposide in both cisplatin and noncisplatin-containing combinations. Early data suggest these combinations display at least additive effects and perhaps some synergy. Ongoing cooperative group trials are evaluating cisplatin/etoposide combinations in minimally pretreated patients with metastatic breast cancer. While trials using high-dose etoposide in combination with other drugs as ablative treatment for breast cancer have been reported, etoposide's poor performance in pretreated patients calls such practice into question; the contribution of etoposide to such therapy is therefore conjectural.