Significance After partial hepatectomy, the adult mammalian liver regenerates through the mobilization of all hepatocytes characterized by a few cycles of cell division and subsequent hypertrophy with loss of global architecture. We have discovered a form of regeneration in the neonatal mouse liver, specific to the first week of life, where we observe numerous rounds of cell division and reconstitution of lobe architecture much like in amphibian limbs. This regenerative process is characterized by clonal expansion of select hepatocyte-specific stem or progenitors that localize to the central vein and is one of the first characterized instances of true mammalian regeneration.