Histologically, the differential diagnosis should be made with primary neuroendocrine carcinoma of the oral cavity and metastatic neuroendocrine carcinoma of the lung, breast, or metastatic Merkel cell carcinoma. The positive immunoreactivity for CDX-2 is confirmatory for the intestinal origin and is preclusive of the other organ sites as possible primaries; furthermore, the lack of dot-like paranuclear expression of CK20 is also not compatible for the diagnosis of Merkel cell carcinoma. This evidence concerns the gene CDX2 and Merkel cell skin cancer.