Background: Patients with metastatic breast cancer (MBC) with disease progression after anthracycline-and/or taxane-containing therapy need an effective drug regimen with low toxicity. Mitomycin C (MMC) and vinorelbine (VNR) are suitable candidates for combination therapy in the second-/third-line treatment of MBC. This study evaluates the safety and efficacy of an MMC/VNR combination chemotherapy in pretreated patients with MBC. Patients and Methods: In a phase II trial, patients with anthracycline-and/or taxane-pretreated MBC were treated with MMC 8 mg/m<sup>2</sup> (day 1) and VNR 25 mg/m<sup>2</sup> (days 1 and 8) every 4 weeks for up to 6 cycles or until disease progression. Results: In 51 eligible patients, 13 (26%) partial remissions (PRs), 20 (39%) stable diseases (SDs) and 18 (35%) progressive diseases (PDs) were observed. The median progression-free survival (PFS) was 5.0 months. The main grade 3/4 toxicities were neutrocytopenia (41%), granulocytopenia (37%), and thrombocytopenia (4%). Other hematological and non-hematological toxicities were mostly mild. Conclusion: The combination of MMC and VNR is an effective and relatively well-tolerated regimen for anthracycline- and/or taxane-pretreated patients with MBC and is suitable for outpatient therapy.