Hepatocellular carcinoma (HCC) is the main cause of death in cirrhotic patients and has become a major health problem in developed countries. Analysis of the somatic alterations and gene expression profiles in patients with HCC have provided important information the genes involved in liver carcinogenesis. Nevertheless, the most important molecular alterations in the initial stages of the disease are currently unknown. The application of high resolution technologies to other forms of cancer (genome analysis with oligo microarrays and SNP arrays) should lead to greater insight into the pathogenesis of this neoplasm. In the last few years, distinct signaling pathways involved in hepatocarcinogenesis have been identified. Among these, the Wnt, EGFR and PI3k/akt/mTOR pathways are constitutively altered in numerous studies, providing the molecular basis for the molecular treatment of this tumor. As in other neoplasms, the original tumor cell in HCC is controversial. The most widely accepted hypothesis suggests that numerous genomic alterations in the hepatocyte cells lead to a neoplastic phenotype. Alternatively, it has been postulated that at least a subgroup of tumors could be of stem cell origin. Both hypotheses agree on the existence of cancer stem cells, arising from the original tumor cell; these cancer stem cells would then perpetuate and disseminate the neoplasm. This review summarizes the most important information on the structural and functional alterations in HCC and describes some of the main signaling pathways implicated in liver cancer.