The use of liver biopsy to diagnose hepatocellular carcinoma is governed by the balance of the risks of the procedure (morbidity, mortality, inadequate sampling), the relative utility of non-invasive techniques and the benefits of precise diagnosis, prognostic and theragnostic information and access to tissue for molecular analysis. In this issue of Hepatology, identification of the macrotrabecular subtype of hepatocellular carcinoma on liver biopsy is shown to add clinically useful prognostic information as well as molecular correlations.