The long latency of malignant mesothelioma, with decades-long chronic inflammation accompanied by an aberrant microenvironment and the presence of ROS and oxidative DNA damage, would advocate a multifactorial mechanism of disease development, with a clear contribution via loss of tumor suppressor genes such as p16 and p19, as reported here. The gene discussed is CDKN2A; the disease is malignant mesothelioma.