Hepatocellular carcinoma (HCC) is characterized by distinct interpatient tumor heterogeneity,1 and patients often respond in markedly different ways to treatment or show drug resistance. This complexity is further emphasized by intratumor heterogeneity (ITH), defined as the morphologic diversity, differential phenotypic potential, and genome variance of distinct tumor cells comprising a single tumor mass. This paradigm of “branched evolution” has emerged as a reflection of the molecular and cellular complexity of advanced liver tumors, complicating accurate classification and clinical management (often innately resistant to therapy at diagnosis).