The incidence of malignant mesotheliomas in Germany has increased since about the mid 1980s, and a further increase is expected until about 2020 due to the peak in asbestos processing in Germany between 1965 and 1980. About 90% of the mesotheliomas recorded in the files of the German Mesothelioma Registry in Bochum are asbestos-related and therefore possibly due to an occupational exposure. In 2003, 717 mesotheliomas were newly diagnosed at the German Mesothelioma Registry. Mesotheliomas are very heterogeneous in terms of histological appearances and of prognosis. At present, the diagnostic gold standard is conventional histology in combination with additional immunohistochemical analysis. We were not able to confirm a promising report that described telomerase reverse transcriptase catalytic subunit (TERT) for the differentiation between reactive and neoplastic mesothelial lesions, which can be extremely difficult. DNA cytometric analysis may also help differentiate between reactive and neoplastic mesothelial lesions. There are some characteristic patterns of chromosomal imbalances as detectable by comparative genomic hybridization (CGH), but at present, specific chromosomal or genetic defects that give rise to a mesothelioma are not known. A reliable pathological diagnosis is the basis for therapeutic, prognostic, and medicolegal consequences. In general, it can be achieved by thoracoscopic inspection with specifically directed biopsy. Furthermore, a description of the peculiarities of each mesothelioma by the pathologist might be the key to a more individual therapy in the future.