CDX2 is a homeobox gene that encodes an intestine-specific transcription factor (1). CDX2 has been useful to establish gastrointestinal origin of metastatic adenocarcinomas and carcinoids and can be especially useful in distinguishing metastatic colorectal adenocarcinoma from tumors of unknown origin (1-7). CDX2 has been shown to be more specific and more sensitive than villin or CK20 (1,4,6). CDX2 has also been shown to be expressed in mucinous ovarian cancer, bladder adenocarcinoma, cholangiocarcinoma and malignant germ cell tumors of the testes (1,2,6-8). Only very rare examples of carcinomas of the genitourinary and gynecologic tracts or breast, lung, and head and neck cancers showed elevated levels of CDX2 expression (1). Recently, a new rabbit monoclonal CDX2 has been developed and studies have shown that CDX2 rabbit monoclonal is a more sensitive clone than other CDX2 mouse monoclonal antibodies. Data has also shown that rabbit monoclonal CDX2 had fewer false negatives (9). The specificity was similar when compared to other mouse monoclonal CDX2 antibodies. However, in certain cancers, rabbit monoclonal CDX2 displayed a slightly higher percentage (9). The overall specificity for CDX2 antibodies can be significantly improved in a panel with CK7, TTF-1 and CDH17 (3,4,6,10).