Both the hepatitis B virus (HBV) and cancer stem cells (CSCs) have been independently implicated in the pathogenesis of hepatocellular carcinoma (HCC). To date, there have been no reports describing HBV infection within CSCs. In this report we describe HBV core (HBcAg) and HBx protein expression within CSCs associated with human HCC. HBV markers were also identified in nonmalignant stem cells present in adjacent nontumor tissue. These findings provide new insights into the pathogenesis of HBV-induced HCC and are potentially relevant to the treatment of both HCC and chronic HBV.