BACKGROUND: CDX2 is a gene involved in the regulation of intestinal cell proliferation/differentiation. It is considered specific for enterocytes and has been used for the diagnosis of primary and metastatic colon adenocarcinoma. The aim of this study was to assess the usefulness of CDX2 in the diagnosis of cutaneous metastatic tumors and extramammary Paget's disease. MATERIALS AND METHODS: The immunohistochemical expression of CDX2 was studied in 68 cutaneous metastatic tumors of various origins and 14 specimens of extramammary Paget's disease. RESULTS: CDX2 expression was found in 3/6 metastases of colon adenocarcinoma, 1/1 metastasis of urothelial carcinoma and 1/2 extramammary Paget's disease. CONCLUSION: CDX2 appears to be specific for cutaneous metastases from intestinal and urothelial carcinomas and is a useful diagnostic marker of these tumors. However, its sensitivity is modest, and we advocate its use in conjunction with additional immunohistochemical markers. CDX2 seems useful for the diagnosis of extramammary Paget's disease associated with an underlying colorectal tumor.