Seizures, coma and death rapidly appeared after admission in a one ‑month‑old foal with a history of lethargy, fever and anorexia. Severe icterus and necrotizing hepatitis were observed at necropsy. Clinical signs, laboratory and postmortem findings were compatible with a suspect of clostridial hepatitis. Tyzzer’s disease was confirmed by the presence of organisms morphologically consistent with Clostridium piliforme in the hepatocytes at the margins of multiple areas of hepatic necrosis. To the authors’ knowledge, this is the first reported case of clostridial hepatitis caused by Clostridium piliforme in a horse in Italy.