Intermediate-sized filament (IF) protein designated Cytokeratin 20 (CK20) is a major cellular protein of mature enterocytes and goblet cells commonly found in mucosal epithelium of the mammalian gastrointestinal tract. Results strongly suggest that transcriptional regulation of keratin genes in the intestinal epithelium occurs at the level of both immature and terminally differentiated epithelial cells, and is tightly regulated during both fetal development and crypt-to-villus differentiation of the intestinal epithelium. CK20 has recently been reported to be useful to distinguish between primary and metastatic lung adenocarcinoma. CK20 expression was significantly more prevalent in adenocarcinoma that originated in the GI tract than that of pulmonary or breast origin. Cytokeratin 20 is often used in conjunction with CK7 and other antibodies in distinguishing colon carcinomas (CK20+) from ovarian, pulmonary, and breast carcinomas.