There is an increasing body of evidence that hepatitis E virus (HEV) triggers acute hepatitis not only in tropical and subtropical regions of Asia, Africa, and America with low sanitary standards but also in highly industrialized countries. We here report on two patients from Thuringia (Germany) with a HEV infection without a recent stay abroad. All other common causes of hepatitis were excluded. Transaminases were significantly incresed in both cases, while icterus could be proven in one patient, only. Both patients fully recovered in the long-term course. Epidemiological and phylogenetic data from viral analyses suggest that HEV infection has to be considered as a zoonosis. It is likely that viral transmission from animals to humans occurs through insufficiently cooked meat or entrails, e.g., from pigs or wild animals. In summary, HEV infection is a relevant differential diagnosis in acute non-A/B/C viral hepatitis. Further studies are required for the identification of other transmission pathways, pathogen reservoirs as well as novel concepts for prophylaxis, especially for patients at risk for hepatic diseases.