Angiopoietin-like protein (ANGPTL) 8 regulates the partitioning of triglycerides by inhibiting lipoprotein lipase in muscle and adipose tissues. ANGPTL8 is expressed in the liver and adipose tissue and secreted into the blood. However, the precise localization of ANGPTL8-expressing cells in these tissues remains unknown. The aim of the present study was to investigate the localization of ANGPTL8-expressing cells in human tissues. Using formalin-fixed paraffin-embedded human tissue specimens, the expression of ANGPTL8 was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC) and in situ hybridization (ISH). The expression level of ANGPTL8 mRNA was the highest in the liver, followed by lipoma, hibernoma and normal adipose tissue. In the liver, wild type (KF809856) and two splice variants of ANGPTL8 mRNA (KF809857 and KF809858) were found to be expressed. The expression level of the splice variant KF809858, which produces a short form of ANGPTL8, accounted for <1% of ANGPTL8 in the liver. IHC revealed that ANGPTL8 was expressed in hepatocytes in zone 1 of the hepatic acinus in the liver. In the adipose tissue, mature adipocytes weakly expressed ANGPTL8, while immature adipocytes strongly expressed it. ISH confirmed ANGPTL8 mRNA expression in portal hepatocytes and immature adipocytes. ANGPTL8 was expressed in the cells, which actively uptake and metabolize triglycerides. In hibernoma, the ANGPTL8 protein and mRNA were homogeneously expressed in tumor cells. The expression of ANGPTL8 was associated with the differentiation state and activity of lipid metabolism in a subpopulation of cells in the liver and adipose tissue. The association may be helpful for the understanding of local metabolic state in organs and diseases associated with the lipid metabolism.