Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer inevitably progressed after a short response to initial trastuzumab treatment, suggesting a possibility of acquired-resistance to trastuzumab. Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI), has been reported as an effective and safe drug for the treatment of HER2-positive relapsed or metastatic breast cancer. Pyrotinib combined with capecitabine is widely used to treat HER2-positive metastatic breast cancer in patients who have been previously treated with anthracyclines, taxanes, and trastuzumab. However, the efficacy of pyrotinib combined with other chemotherapy drugs is still unclear. Here we report pyrotinib combined with carboplatin in treating a patient with HER2-positive relapsed breast cancer who had acquired resistance to trastuzumab. The patient received three cycles of treatments of pyrotinib (400 mg, orally once per day, days 1-21) combined with carboplatin (600 mg, iv drip, day 1, cycled every 21 days). The patient showed an excellent response to the therapy, including faded rashes on the skin of her breast, no obvious signs of recurrence from the breast magnetic resonance imaging (MRI), decreased skin thickness and cord shadow of the right breast, unchanged degree of right pleural effusion, and no enlarged LN. The patient had a stable disease time of more than four months. Our case provides evidence for the feasibility and efficacy of pyrotinib with carboplatin in treating patients with HER2-positive relapsed or metastatic breast cancer who may develop resistance to trastuzumab.