Hepatitis E virus (HEV) is the main cause of enterically transmitted non-A hepatitis worldwide. Infection is endemic in developing countries. Disease course is benign, and severe jaundice is rarely reported. Three patients presented to our department with symptomatic acute hepatitis. Two of them had recently travelled to endemic areas. Jaundice was very marked in all patients. HEV infection was documented by HEV antibodies and by HEV-RNA detection in serum and stools. In the autochthonous case, immunoglobulin-M was absent, and diagnosis was established on HEV-RNA amplification by real-time reverse transcriptase-PCR. Comprehensive investigation for concomitant causes of liver disease was negative in all patients. Histological features showed marked cholestasis with multiple bile plugs in dilated canaliculi. In conclusion, acute hepatitis E may be autochthonous in developed countries and patients may present with severe jaundice. HEV-RNA detection by real-time reverse transcriptase-PCR is a very efficacious diagnostic tool in anti-HEV immunoglobulin-M-negative cases.