Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related mortality worldwide and has a well-defined etiology. It develops in a stepwise process with morphologically defined precursor lesions. Typing of highly differentiated hepatocellular tumors is supported by immunohistological marker panel and the so-called matrix diagnosis. The recent World Health Organization (WHO) classification defined morpho-molecular HCC subtypes showing typical clinical and prognostic characteristics. If HCC subtyping is considered in future clinical studies of advanced HCC, this could help to introduce personalized HCC therapy. Currently, precision oncology is not available for HCC.