The pathologist who sees specimens from lesions of the serosal membranes (pleura, pericardium, peritoneum, and tunica vaginalis) is well aware that these cases, whether in the form of fluid cytologies, small biopsies, or major resections, pose differential diagnostic problems that are among the most difficult in anatomic pathology. The main problems involve the separation of malignant mesothelioma from benign mesothelial processes on the one hand and other malignant tumours (particularly primary and metastatic carcinomas) on the other. With these differential diagnoses in mind, the authors concentrate on the cytopathologic and histopathologic features of diffuse malignant mesothelioma, its many variants, and the other benign and malignant lesions to be distinguished from it. Histochemical, immunohistochemical, ultrastructural and molecular features of potential use in this differentiation are discussed and illustrated. Common differential diagnostic problems and their solutions take precedence, but all of the known benign and malignant lesions of serosal membranes are covered, with copious illustrations and the latest available references. Epidemiologic, pathogenetic, clinical, radiographic and gross pathologic features are integrated with the discussions of these entities. This will be the most complete source available on this topic for years to come.