AbstractWe have reviewed the effusion cytology of 51 cases of histologically proven malignant mesothelioma of the pleura (49 cases) and the peritoneum (2 cases). The patient group included 45 males and 6 females, aged 45‐83 yr. A cytological diagnosis of malignancy had been rendered on 43 cases, and in 30 of them it was consistent with, or at least suggestive of, a mesothelioma. Diagnostic clues, especially evident in epithelial and biphasic tumors were hypercellularity and/or morular aggregates of malignant cells showing scalloped borders and nuclei with dense chromatin and evident nucleoli. Cytomegaly with multinucleation was also frequently observed. Reactive mesothelial cells were often present along with other non specific features such as red blood cells, fibrin, necrotic debris. In 13 cases, a diagnosis of malignancy was entertained but mesothelioma, although considered, was not reported out because of scantiness of material. In four cases, adenocarcinoma was erroneously diagnosed for the presence of deceptive cell vacuoles. In eight cases, no diagnostic cells were recovered in repeated effusions. The first diagnosis was a cytologic one in 37 patients. Tissue study was performed on autopsy (35 patients) and surgical material. The latter was the only source of histology in six cases. Immunocytochemical investigation was negative for carcinoembryonic antigen in all but one tested cases (1/21) and positive for human milk fat globulin in about one‐half of the epithelial and biphasic tumors. In 18 of 21 cases, positivity for combined high‐and low‐molecular‐weight keratins was detected. The results of our survey indicate that conventional cytology permits accurate identification of either reactive and neoplastic mesothelial cells. The distinction between mesothelioma and adenocarcinoma may be further attempted using immunocytochemistry, combining a few commonly available markers, although the results should be carefully evaluated in view of their lack of sp