This study provides a guideline to a dynamic approach toward the diagnosis of hepatocellular carcinoma (HCC). Bile production, fibrinogen synthesis, Mallory body, fibrinogen ground-glass and abnormal glycogen bodies as a reflection of "clone" selection, and hepatitis B virus (HBV) antigen expression in tumor cells can be considered as markers for the morphological diagnosis of HCC. The demonstration in tumor cells of these diagnostic features requires a careful screening of routinely stained preparations in search of suggestive, characteristic, specific, or pathognomonic features further supplemented by ancillary techniques, such as histochemistry, immunocytochemistry, and electron microscopy.