The purpose of this study was to evaluate the efficacy (progression free survival (PFS) and response rate) and safety of vinorelbine and trastuzumab combination chemotherapy in patients with HER2-overexpressing, metastatic breast cancer as a first line chemotherapy regimen. Patients with histologically confirmed, HER2-positive (immunohistochemistry (ICH) 3+, or 2+ and FISH+) metastatic breast cancer who had nor received prior vinorelbine or anti-HER2 therapy in the adjuvant setting, received at least eight weeks of vinorelbine i.v. (25 mg/g weekly) and trastuzumab (4 mg/kg on day 1 followed by 2 mg/kg weekly). Forty-one women from six participating centers were enrolled into the trial. The overall response rate, was 43.9% (18 of 41 patients), (CI 28-60.3%), 30% of patients were progression free after 1 year. Four patients reached complete remission, 14 partial remission and five had stable disease for at least 18 weeks. Six patients developed primary progression. 35 patients (85%) experienced progression after a median time of 235 days. Therapy was in general well-tolerated. There were two CTC grade 4 infusion syndromes and two patients experienced cardiotoxicity at least grade 2. This phase II trial of vinorelbine and trastuzumab demonstrated an effective and well-tolerated regimen with a favourable safety profile.