Hepatocytes, the cells of the liver that provide most of its functions, typically regenerate themselves. However, in chronic liver diseases the regenerative capabilities of hepatocytes can be overwhelmed. Under these conditions liver stem cells are thought to serve as a backup system by producing new hepatocytes. Our study failed to find evidence for liver stem cell-derived hepatocytes in mice, which argues against the existence of liver stem cells and highlights the importance of the regenerative capabilities of hepatocytes.