We report three cases of severe hepatotoxicity related to benzarone, a benzofuran derivative. Our cases include a 35-year-old woman with (sub)fulminant hepatitis, a 67-year-old woman with macronodular cirrhosis, and a 68-year-old man with severe chronic active hepatitis and cirrhosis, with positivity of anti-smooth muscle antibodies. Two patients died. We stress the potential of benzarone to cause hepatotoxicity, which usually resembles severe chronic active hepatitis. Our cases constitute the most severe cases of benzarone hepatotoxicity reported so far, and comprise the first cases of (sub)fulminant hepatitis and cirrhosis related to benzarone.