In spite of the heterogeneity of HCC, tumor onset and progression have been associated with recurring cell-autonomous molecular changes [5] such as the loss of expression of differentiation genes (e.g., Hepatocyte Nuclear Factor 1 and 4, HNF1α, and HNF4α) [6,7], chromosomal instability leading either to the loss of heterozygosity in tumor suppressor genes (e.g., p. 53) [8] or to the amplification of loci for oncogenes (e.g., ERK5) [9], and aberrant activation of signaling pathways (e.g., Wnt/β-catenin pathway) [10]. The gene discussed is HNF4A; the disease is neoplasm.