A large number of immunohistochemical markers that can assist in the differential diagnosis of epithelioid mesotheliomas are currently available. Because these markers are expressed differently in the various types of carcinomas that can metastasize to the serosal membranes and can potentially be confused with epithelioid mesothelioma, their selection for inclusion in a diagnostic panel largely depends on the differential diagnosis, as well as on which ones work the best in a given laboratory. Traditionally, the panels used in the differential diagnosis of epithelioid mesotheliomahave consisted of a combination of positive mesothelioma markers and broad-spectrum carcinoma markers. At present, a wide variety of organ-associated carcinoma markers such as thyroid transcription factor-1 and napsin A for the lung, PAX 8 and PAX 2 for the kidney, and Müllerian-derived tumors; gross cystic disease fluid protein-15 and mammaglobin for the breast; and CDX2 for intestinal differentiation are available, which can assist in establishing the site of origin of an adenocarcinoma when included in a diagnostic panel. This article provides updated information on the composition of the panels of markers recommended in the various differential diagnoses.