<b><i>Introduction:</i></b> Carcinoma ex pleomorphic adenoma (CXPA) of the salivary glands has often a salivary duct carcinoma (SDC) component, which resembles ductal carcinoma of the breast and frequently overexpresses human epidermal growth factor receptor-2 (HER2). We report a case of metastatic CXPA with SDC component who was treated with trastuzumab-based chemotherapy and has had a durable complete response. <b><i>Case Report:</i></b> A 74-year-old man was diagnosed with CXPA of the right parotid gland. The resected tumor was histologically diagnosed as CXPA with a predominant SDC component that showed strong positivity for HER2 protein and <i>HER2</i> gene amplification. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with paclitaxel and trastuzumab was initiated. A complete response was confirmed after 7 treatment cycles, and no evidence of disease progression has been observed after 13 months of initiation of therapy. <b><i>Conclusions:</i></b> This report suggests a potential utility of trastuzumab-based chemotherapy for HER2-positive CXPA.