Hepatitis C virus (HCV) infection is diagnosed by initial testing of antibodies to hepatitis C virus (anti-HCV). Antibodies of the IgM class to HCV appear earlier than anti-HCV IgG and they persist for a few months with high titres. At the same time, anti-HCV IgM is usually found in almost all patients with acute hepatitis C and during acute exacerbation of chronic hepatitis C, which correlates to persistent viremia. Despite the fact that polymerase chain reaction (PCR) is considered as the gold standard for detection of HCV viremia, some limitations exist connected to the technical performance and costs of the test. In this study we have evaluated the detection of anti-HCV IgM antibodies as a marker of viral replication in HCV positive patients. We have detected the presence of anti-HCV IgM antibodies in all RNA positive samples. The detection of both anti-HCV and anti-HCV IgM antibodies as a first step before the testing of HCV RNA is proposed for the detection of viral replication in clinical settings.