The frequent occurrence of metastases from the primary tumor present a major therapeutic problem in hepatocellular cancer because of the hematogenous spread of cancer cells. Standard imaging diagnostics methods do not allow for an early detection of relapse of the disease, as opposed to the analysis of molecular cell markers, especially mRNA-based methods, in peripheral blood samples by RT-PCR. Analysis of alphafetoprotein expression is the "gold standard" in the diagnostics of HCC at the protein and mRNA level because of its specificity for liver cancer. However, working out an analysis protocol is problematic and the utility of the marker in monitoring a patient's status in the perioperative period remains controversial. New HCC markers are being searched for among the highly liver-specific ones and those shared between various cancers types. Markers associated with freely circulating nucleic acids are also studied and quantitative assays are used. An assay for several markers simultaneously could give satisfactory results.