The classical morphological criteria in the diagnosis of hepatocellular carcinoma (HCC) include: a) the similarity of tumour cells to hepatic cord cells; b) the trabecular nature of the growth with capillary and canaliculi formation; and c) the intravascular growth of trabecular carcinoma. These criteria apply to the most common variants of HCC but they do not define all cases of HCC. That makes additional criteria and certain refinements necessary. A promising approach to the diagnosis of HCC is that based upon the consideration by the pathologist of some relevant aspects of the natural history of this tumour. A panel of tests exploring the various functions and properties of liver cells should be developed. This study provides a guideline to a dynamic approach in the diagnosis of HCC. The rationale is based on 5 points; among them, bile production, fibrinogen synthesis, Mallory body, fibrinogen G-G selection and HBV antigen expression can be considered at present as confident markers for the morphological diagnosis of HCC.