Here, we describe a de novo, hepatitis C-related combined cholangiocellular and hepatocellular carcinoma with marked intratumor heterogeneity on three levels: morphology, immunohistochemical marker profile and mutational status with 3/14 tumor regions of solely hepatocellular differentiation harboring concomitant mutations of CTNNB1 and TP53. The gene discussed is CTNNB1; the disease is hepatocellular carcinoma.