Background/Aim: The aim of this study was to assess the incidence of MSI in a large series of human hepatocellular carcinomas (HCC) with various etiologies. Materials and Methods: The MSI status was determined by polymerase chain reaction (PCR) using 5 mononucleotide and 13 CAn dinucleotide repeats. Results: None of the 122 HCC samples displayed an MSI-High phenotype, as defined by the presence of alterations at more than 30% of the microsatellite markers analyzed. Yet, limited microsatellite instability consisting in the insertion or deletion of a few repeat motifs was detected in 32 tumor samples (26.2%), regardless of the etiology of the underlying liver disease. MSI tended to be higher in patients with cirrhosis (p=0.051), possibly reflecting an impact of the inflammatory context in this process. Conclusion: Based on a large series of HCC with various etiologies, our study allowed us to definitely conclude that MSI is not a hallmark of HCC.