Biopsy diagnosis of early and highly differentiated liver tumors is one of the most challenging tasks in histopathology. During recent years its parameters have changed fundamentally due to shifting clinical algorithms. Modern histopathology has met this challenge by defining new, prognostically relevant subtypes of early hepatocellular carcinoma and by elaborating morphological algorithms and novel immunohistological markers for the differential diagnosis of highly differentiated hepatocellular tumors. In addition, a new, predictive molecular pathological and histological classification of liver cell adenoma has been developed. By means of the consequent application of these new diagnostic tools, together with the so-called 'matrix diagnosis', a reliable diagnosis is achieved in the vast majority of these difficult cases.