Abstract: Intrahepatic cholangiocarcinoma (iCCA) is an epithelial malignancy with a poor prognosis and an ever-increasing morbidity and mortality rates in recent years. Chemotherapy-based standard treatment is ineffective, and novel effective precision treatment strategies are urgently needed. However, iCCA is characterized by high heterogeneity in tissue morphology and molecular profiles, which is a considerable obstacle to clinical precision therapy. Tumor heterogeneity develops due to the interaction of multiple complex factors, including pathogenic factors, different genetic mutations, plasticity in molecular profiles, and different potential origin cells. Current genetic lineage tracing systems in mouse models have identified bile duct cells, hepatocytes, and hepatoblasts as possible origin cells of iCCA. This systematic review of the relevant studies on these tumor origin cells suggests that integrating the relevant information about iCCA on origin cells into current histopathological and molecular classification system should help guide the precise diagnosis and treatment of iCCA.