Claudins are tight junction proteins that are critical for the sealing of cellular sheets and controlling paracellular ion flux. The claudin family of proteins is composed of at least 24 closely related transmembrane proteins, most of them are well characterized at the gene and protein levels. The claudins are present in variety of normal tissues, hyperplastic conditions, benign neoplasms, and cancers that exhibit epithelial differentiation. Loss of claudins expression has also been reported in several malignancies as well. Differential expression of various members of the claudins family in cancers can be used in confirming the histologic identity of certain cancers and excluding others. Examples include the use of immunohistochemical detection of claudins to differentiate between oncocytoma and chromophobe renal cell carcinoma, endometrial endometrioid carcinoma and seropapillary carcinoma, mesothelioma and metastatic adenocarcinoma, hepatocellular and biliary tract carcinomas, and between intestinal-type and diffuse-type gastric carcinoma. Expression of certain claudins can also be used as markers that can predict patient’s prognosis. Thus, it seems that attempts to identify expression claudins in cancers are becoming increasingly useful in histologic diagnosis of tumors as well as means to assess patient’s prognosis.