The combination of vinorelbine and trastuzumab (VH) is highly active and well tolerated in patients with metastatic HER2+ breast cancer. We assessed the efficacy and tolerability of VH as an alternative adjuvant treatment for patients with localized breast cancer refusing or ineligible for standard adjuvant trastuzumab-based chemotherapy. Twenty-eight patients with stage I-III breast cancer were treated only with VH as preoperative or postoperative chemotherapy. Fourteen patients received VH as adjuvant treatment for pT1a-b pN0 or eR+ pT1c pN0 cancers. VH was well tolerated, the only grade 3-4 toxicity being neutropenia with 2 cases of febrile neutropenia. At a median follow-up of 39 months, no breast cancer relapses were documented; moreover, overall and disease-free survival was 96.4%. In summary, our results indicate that VH is effective and well tolerated. VH should be prospectively tested as adjuvant treatment for pN0 pT1a-b breast cancer patients for which no standard treatment is well defined.