The current metastasis paradigm suggests that the primary tumor starts off benign but over time slowly acquires changes that provide a few rare cells within the tumor the ability to metastasize. However, this concept has been challenged by several recent studies using the microarray-based approach. We have recently found that the molecular signature of primary hepatocellular carcinoma (HCC) is very similar to that of their corresponding metastases, while it differs significantly in primary HCCs with or without metastasis. Similar findings are also evident in primary cancers of the lung, breast, and prostate. Such a signature can be used to predict the prognosis of HCC patients. Moreover, there are significant differences in the gene expression profiles of liver parenchyma among HCC patients with or without intrahepatic metastases. These findings imply that many of the metastasis-promoting genes are embedded in the primary tumors and that the ability to metastasize may be an inherent quality of the tumor from the beginning. In addition, the condition of liver parenchyma may dictate the intrahepatic metastasis potential, which is consistent with the hypothesis that the degree of viral-hepatitis-mediated liver damage or possibly the genetic makeup of individuals may play an important role in metastasis.