Hepatitis E virus (HEV) genotype 3 is an emerging pathogen in the developed world. As the clinical manifestations and routine laboratory parameters are often nonspecific, accurate diagnostic tests are crucial. In the current study, the performance of six serological assays and three PCR assays for the detection of HEV was evaluated. In the setting of the Ghent University Hospital, patients with clinically suspected HEV infection were tested for the presence of HEV IgM and IgG as well as HEV RNA. Serology was performed using six commercial HEV ELISA assays: Biorex, Wantai and Mikrogen IgM and IgG. HEV RNA was detected using one commercial assay (Altona RealStar®), and two optimized in-house real-time RT-PCR assays (according to Jothikumar et al., 2006 and Gyarmati et al., 2007). In addition, all three PCR assays were performed on 16 external quality control (EQC) samples. In a period of 39 months (January 2011-April 2014), 70 patients were enrolled. Using different ELISA assays, the prevalence of antibodies varied from 5.7% to 14.3% for HEV IgM and from 15.7% to 20.0% for IgG. All but two of the results of the PCR assays performed on clinical samples agreed. However, 10 out of 16 EQC samples results showed major discrepancies. We observed important differences in the performance of various serological and PCR assays. For this reason, results of both serological and molecular tests for HEV should be interpreted with caution.