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Salivary gland neoplasms (SGNs) respond poorly to the traditional chemotherapy agents limiting the availability of systemic treatment options in the metastatic setting. The recent identification of actionable molecular targets in SGNs has led to the evaluation of targeted therapies in non-approved advanced SGNs. We present the case of an elderly male with HER-2 Neu overexpressing metastatic mucoepidermoid carcinoma (MEC) who demonstrated a prompt and sustained disease response to targeted therapies directed against HER-2 Neu with long survival inte