Mesothelioma is a relatively rare malignant neoplasm arising from the serosal lining of the pleural, peritoneal, and pericardial cavities. Mesotheliomas are known to be associated with asbestos exposure. The karyotypes of these tumors have mostly been so complex as to preclude the identification of primary chromosome abnormalities. We present the cytogenetic analysis of two macroscopically distinct abdominal tumors, both diagnosed as peritoneal mesothelioma, occurring in a woman with a history of heavy asbestos exposure. Both tumors contained the same three karyotypically abnormal but cytogenetically related clones, with a balanced t(3;3)(p14;q29) as the primary chromosomal change. The fact that several chromosome abnormalities were common to both tumors strongly indicates that they arose through intraperitoneal spreading of a single neoplastic process; that is, they were not pathogenetically independent lesions. Our findings, taken together with previously published cytogenetic data on peritoneal mesotheliomas, indicate that a proportion of these tumors may be characterized by simple, balanced chromosomal rearrangements. At least a subset of peritoneal mesotheliomas arises through the same pathogenetic mechanisms that are involved in the pleural forms of this disease.