Abstract Malignant pleural mesothelioma (MPM) is known to be a clinical and pathological challenge. Its incidence is continued to increase worldwide including Egypt unfortunately. There is a positive link between the residential location and the incidence of mesothelioma. It is commonly occurring in areas of heavy pollution and environmental exposure to asbestos. Most of MPM cases are strongly suspected on routine hema-toxylin & eosin staining. They exhibit a variety of histologic subtypes: Epithelioid, sarcomatoid or biphasic type. Epithelioid type of MPM can be easily confused with metastatic adeno-carcinoma. Although immunohistochemistry has proven to be valuable in the differentiation of epithelioid mesothelioma from metastatic adenocarcinoma, no single antibody has demonstrated absolute sensitivity or specificity in making this distinction. Using immunohistochemical analysis with D2-40, a monoclonal antibody that has been used as a lym-phatic endothelial marker may be useful in the differential diagnosis of epithelioid mesothelioma versus metastatic adenocarcinoma because of its staining of mesothelial cells. D2-40 had been reported to have strong membranous immu-nostaining in up to 96% of MPM and reactive mesothelial processes but negative staining in adenocarcinoma.