Aim of the Commentary is to go through some of them and bring the focus particularly on the information deriving from the paper by Pinon et al. in this issue of the Journal, which paves the way to the inclusion of the hepatocyte nuclear factor-1-beta deficiency as a new condition to consider in the diagnostic process of the syndromic forms with paucity of intralobular bile ducts.<h4>Conclusion</h4>Neonatal cholestasis poses diagnostic challenges in practice. This evidence concerns the gene HNF1B and cholestasis.