Intestinal-type adenocarcinoma (ITAC) is a rare form of sinonasal cancer characterized by an association with exposure to industrial dusts, aggressive clinical behavior, and histologic/immunophenotypic similarity to tumors of the gastrointestinal tract. ITAC is sometimes very poorly differentiated and difficult to distinguish from other sinonasal neoplasms, particularly in a limited biopsy. CDX-2 and cytokeratin 20 are consistently immunoreactive in ITAC and as a result, these immunostains are often used to support the diagnosis. However, CDX-2 and cytokeratin 20 have not been tested on a broad range of sinonasal tumors, so their specificities remain unknown. Immunohistochemistry for CDX-2 and cytokeratin 20 was performed on 6 sinonasal ITACs as well as 176 non-intestinal-type sinonasal neoplasms. CDX-2 and cytokeratin 20 were positive in all 6 cases of ITAC. CDX-2 immunoexpression was also observed in 17 of 176 (10 %) non-intestinal-type tumors including 6 of 16 (38 %) sinonasal undifferentiated carcinomas, 8 of 81 (10 %) squamous cell carcinomas (including 5 of 39 non-keratinizing variants), 2 of 20 (10 %) salivary-type adenocarcinomas, and 1 of 2 (50 %) small cell carcinomas. In contrast, among non-intestinal types of sinonasal tumors, cytokeratin 20 was only focally observed in 1 of 176 non-intestinal tumors (a non-keratinizing squamous cell carcinoma). All cases of non-intestinal surface-derived adenocarcinoma and esthesioneuroblastoma were negative for both markers. Both CDX-2 and cytokeratin 20 are highly sensitive for the diagnosis of sinonasal ITAC, but cytokeratin 20 is more specific. CDX-2 staining may be observed in other high grade tumor types, especially sinonasal undifferentiated carcinoma and non-keratinizing squamous cell carcinoma. As a result, in the setting of a poorly differentiated sinonasal carcinoma the diagnosis of ITAC should not be based on CDX-2 immunoexpression alone. Clear-cut glandular differentiation and cytokeratin 20 immunoexpression are more reliable features.