In a recent Nature Genetics letter, entitled “Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas,” Nault and colleaguesdocument that of 193 patients with hepatocellular carcinoma (HCC), 11 contained an integrated genome sequence of the wild-type adeno-associated virus 2 (AAV2), and suggest that AAV2 is associated with oncogenic insertional mutagenesis in human HCC. Because AAV2 has long been known to be a nonpathogenic human parvovirus and, in fact, has been shown to possess antitumor activity, it is critical that the scientific and clinical implications of these studies be rigorously assessed to justify their conclusions. We have carefully analyzed the data presented by Nault and colleaguesand reached a conclusion that is at variance with that of the authors.