Mesothelioma, literally “tumor of the mesothelium,” is a term often used synonymously with malignant (diffuse) mesothelioma, the malignant neoplasm arising from the serosal linings of the pleural, pericardial, or peritoneal cavities. These major body cavities are lined by a single layer of flattened to cuboidal cells of mesodermal origin that constitute the mesothelium proper [1]. This serosal membranous lining includes not only the mesothelium but also the underlying basement membrane, a matrix of elastic fibroconnective tissue containing lymphatic and vascular channels, and scattered mesenchymal cells as well. Mesothelial cells possess a complex cytoskeletal network of intermediate filaments, produce hyaluronic acid, and have distinctive ultrastructural features including numerous pinocytotic vesicles and long surface microvilli that project into the serous cavities (Fig. 5.1) [2, 3]. It remains uncertain whether mesothelioma results from the malignant transformation of the differentiated mesothelial cell or from more primitive progenitor cells, such as the submesothelial mesenchymal cell, or from both [4].