The cellular origin of tumors remains as one of the unanswered, fundamental questions of cancer biology. The notion that tumors may arise from tissue stem cells is supported by phenotypic similarities between these two cell types, such as proliferative potential and expression of onco-fetal proteins. Liver stem cells, or oval cells, have been put forth as a possible target for hepatocarcinogens. Genetically modified and in vitro transformed oval cells have been shown to form tumors in transplantation to animals. Chemical carcinogenesis models in the liver demonstrate varying degrees of oval cell proliferation. There is also preliminary evidence that hepatocellular carcinoma may maintain a bipotential phenotype consistent with an oval cell origin. Whereas definitive proof of an oval cell origin of hepatocellular has yet to be presented, the current circumstantial evidence justifies continued research on this subject.