Leptospirosis is probably the most widespread and prevalent zoonotic disease in the world and it is difficult to diagnose. Therefore, the disease is frequently not recognized and consequently severely neglected. This infectious disease is re-emerging globally and numerous outbreaks have occurred worldwide during the past decade. It may occur wherever the risk of direct or indirect exposure to urine or kidneys of infected animals is present. Leptospirosis is likely to be underestimated because many patients have mild or subclinical infection and serological testing is imperfect and not always performed. Here it is presented a fatal case of Leptospirosis in Sicily, occurred at the Internal Medicine Division of the University Hospital of Palermo