This paper presents two human cholangiocarcinoma organoid lines and their value in preclinical cancer research, one of them (P68) generated from metastatic iCC without common oncogenic driver mutations in KRAS, TP53, IDH1, or ARID1A. After optimization of the culture medium, organoid cultures could be maintained for extended periods of time. This evidence concerns the gene TP53 and intrahepatic cholangiocarcinoma.