The study investigates the genetic predisposition to malignant mesothelioma, a cancer primarily linked to asbestos exposure. The authors identified germline mutations in the *BAP1* gene in two families with a high incidence of mesothelioma, suggesting a genetic basis for this cancer. Somatic *BAP1* alterations were also observed in familial mesotheliomas, indicating biallelic inactivation. Additionally, some *BAP1* mutation carriers developed uveal melanoma, and germline *BAP1* mutations were found in two out of 26 sporadic mesotheliomas, both of which had a history of uveal melanoma. Truncating mutations and aberrant BAP1 expression were common in sporadic mesotheliomas without germline mutations. These findings suggest a *BAP1*-related cancer syndrome characterized by mesothelioma and uveal melanoma, with potential involvement of other cancers. The study highlights the importance of early intervention for individuals at high risk of mesothelioma due to *BAP1* mutations.The study investigates the genetic predisposition to malignant mesothelioma, a cancer primarily linked to asbestos exposure. The authors identified germline mutations in the *BAP1* gene in two families with a high incidence of mesothelioma, suggesting a genetic basis for this cancer. Somatic *BAP1* alterations were also observed in familial mesotheliomas, indicating biallelic inactivation. Additionally, some *BAP1* mutation carriers developed uveal melanoma, and germline *BAP1* mutations were found in two out of 26 sporadic mesotheliomas, both of which had a history of uveal melanoma. Truncating mutations and aberrant BAP1 expression were common in sporadic mesotheliomas without germline mutations. These findings suggest a *BAP1*-related cancer syndrome characterized by mesothelioma and uveal melanoma, with potential involvement of other cancers. The study highlights the importance of early intervention for individuals at high risk of mesothelioma due to *BAP1* mutations.