Our study shows that hepatocytes can become cholangiocytes and form a functional biliary system in mice that are born without the biliary system. This ability is remarkable because hepatocytes are responsible for providing the liver’s synthetic and metabolic functions, including producing bile, whereas the main function of cholangiocytes is to form tubes that transport bile out of the liver into the intestine. Viewed together with recent findings that cholangiocytes can become hepatocytes if their ability to regenerate themselves is impaired, as in chronic liver diseases, our study suggests conversion of hepatocytes into cholangiocytes and vice versa as the main backup mechanism for liver regeneration. This mechanism could be harnessed for therapy of liver diseases in which cholangiocytes or hepatocytes are lacking or functionally impaired.