P-Glycoprotein and C-MOAT are important hepatic transport proteins which play a role in handling anticancer drugs. Hepatocellular carcinoma is a common hepatic malignancy that is relatively resistant to chemotherapeutic drugs. We therefore studied the expression of these two transport proteins in liver sections from hepatocellular carcinoma by immunohistochemistry and compared the reactivity to that in other liver conditions, including cirrhosis and dysplasia. We studied 53 sections from 17 liver specimens and found that the majority of samples stained positively for both P-glycoprotein and C-MOAT; however, the degree of staining was less in HCC and hepatic adenoma than in liver adjacent to HCC or in cirrhosis or dysplastic nodules. HCC with a compact pattern had less staining than those with acinar, scirrhous, or trabecular patterns. The location of both P-glycoprotein and C-MOAT staining was a function of the liver lesion present. Thus, most tissues without hepatocellular carcinoma showed foci of globular canalicular staining, whereas a delicate linear pattern of canalicular staining was most common overall. We conclude that expression of P-glycoprotein and C-MOAT, as detected by qualitative immunohistochemical evaluation are little affected by the development of HCC and therefore are probably of little clinical significance for management of malignancy.