Subsets of mesothelioma have unusual genetic alterations: genomic near-haploidization in rare pleural mesotheliomas with mutations in <i>TP53</i> and/or <i>SETDB1</i>; oncogenic <i>EWSR1-ATF1</i> fusion; <i>ALK</i> rearrangements in rare patients with peritoneal mesothelioma. The gene discussed is TP53; the disease is peritoneal mesothelioma.