A detailed understanding of the genetic background of hepatocellular carcinoma (HCC) will be crucial to developing new therapies aimed at selected targets.1 Given the sparse treatment options of advanced HCC, such progress is needed urgently for this highly prevalent cancer. However, even though the full genomes of roughly 500 HCC samples are now fully available from diverse sequencing efforts and public databases,2–4 the genetics of HCC remains challenging. This is mostly owing to the significant heterogeneity of these tumors and the experimental/diagnostic problem of a lack of disease-free control liver tissue.