The circulation of liver-derived cells in patients with hepatocellular carcinoma (HCC) has been demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Contrasting results have been reported until now about the clinical impact of these assays, mainly due to technical differences. The use of RT-PCR approaches is now clearly, not suitable for recognition of circulating tumorous cells (CTC) when the test is performed after invasive medical or surgical procedures. Furthermore, the RT-PCR approach is incapable of analyzing the expression of invasion-related genes in CTC. Recently, new assays have been proposed to isolate CTC. They allow immunomorphological and molecular characterization of individual tumor cells. Based on these new results, new therapeutic approaches of metastases should be developed in the near future.