Although it is generally accepted that immunohistochemistry can assist in distinguishing between epithelial mesotheliomas and metastatic adenocarcinomas to the serosal membranes, a great deal of controversy exists regarding not only the practical value of some of the markers currently used, but also which should be included as part of the routine diagnostic panel. Until recently, these panels consisted primarily of antibodies that stained adenocarcinomas but not mesotheliomas. Over the last few years, however, markers that are commonly expressed in mesotheliomas but not in adenocarcinomas have been recognized. The focus of this review is on those markers for which there is an indication that they have a practical use in the diagnosis of mesothelioma. Special emphasis is placed on those which have been most recently recognized.