According to the 2022 International Consensus Classification (ICC) for myeloid neoplasms, multi-hit TP53 is defined either as (a) ≥2 pathogenic TP53 events, such as two mutations, mutation plus deletion, or mutation plus cnLOH, each with a VAF ≥ 10%; (b) a single TP53 mutation with VAF ≥ 50%; (c) a single TP53 mutation with VAF ≥ 10% and either del (17p13.1), cnLOH at 17p, or a complex karyotype [52]. The gene discussed is TP53; the disease is intrahepatic cholangiocarcinoma.