High-grade neuroendocrine carcinoma of the salivary glands is a rare malignancy that can be difficult to distinguish from metastatic neuroendocrine (Merkel cell) carcinoma of the skin, which often occurs on the head and neck and may metastasize to lymph nodes in or adjacent to salivary glands, particularly the parotid gland. As the 2 tumors have morphologic and immunophenotypic overlap, additional diagnostic tools may be clinically useful. Merkel cell carcinoma is known to harbor Merkel cell polyomavirus in up to 80% of cases. However, the presence or absence of this virus in salivary gland neuroendocrine carcinomas has not been investigated. We evaluated 7 primary salivary gland high-grade neuroendocrine carcinomas (all from the parotid) for the virus by both immunohistochemistry (CM2B4 clone) and real-time polymerase chain reaction directed against the conserved small T antigen. Five of the tumors had small cell morphology, and 2 had large cell morphology. All were either chromogranin and/or synaptophysin positive. Four of the 5 small cell (80%) and 1 of the 2 large cell (50%) carcinomas were cytokeratin 20 positive. All but 1 case had cervical lymph node metastases at presentation. Merkel cell polyomavirus T antigen was not detected in any of the 7 tumors, either by immunohistochemistry or by polymerase chain reaction with adequate controls. These observations suggest that primary parotid high-grade neuroendocrine carcinoma arises from a biological pathway that is different from that of cutaneous Merkel cell carcinomas. Furthermore, viral testing may aid in distinguishing the 2 tumor types, as a positive result would favor a metastasis.