Backround/Aim. The final diagnosis of malignant pleural mesothelioma is made exclusively by histopathological examination of biopsy materials that are routinely complemented by the use of immunohistochemical analysis. The aim of this paper was to determine the significance of immunohistochemical analysis and application of certain antibodies in the diagnosis of malignant pleural mesothelioma. Methods. This retrospective analysis included clinical data of 32 patients with the histopathological diagnosis of malignant pleural mesothelioma made in the period 2004-2009 at the Institute for Pulmonary Diseases in Sremska Kamenica. The material was processed and analyzed at the Center for Pathology. Results. CK5/6 was positive, in 63% of the cases calretinin, in 94% and HBME-1 in 80% of the cases. CK7 was positive in 78%, and EMA in 83% of the cases. All the cases (100%) were negative for TTF-1, CEA, CD20, desmin and MOC31. Conclusion. Immunohistochemistry has become an essential diagnostic procedure for the diagnosis and determination of the type of malignant pleural mesothelioma, and due to the lack of individual antibodies a combination of antibody with different sensitivity and specificity is in use today.