Objective: The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma. Method: Paraffin-embedded blocks from surgical material of 19 pleural epithelial mesotheliomas and 22 pulmonary adenocarcinomas were retrieved from the files in our department. The primary antibodies used in each case were the following: antibody anticalretinin, EMA; CEA, BerEP4, TTF-1 and CD15. Results: Of the mesotheliomas, 100 % stained for calretinin, 63.2 % for CK5/6, 78.9 % stained for EMA and AE1/AE3. Of the lung adenocarcinomas, 9.1 % cases showed reactivity for calretinin, 27.3 % for CK5/6, 77.3 % for CD 15, all for TTF-1, 50 % for CEA, 59.1 % for Ber-EP4, 90.1 % for EMA, and all for AE1/AE3. Conclusion: Calretinin were the highly specific positive mesothelial markers, whereas CK 5/6 showed high sensitivity but low specificity. Among negative markers, we advocate the use of TTF-1, CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.