Understanding the molecular subtypes of cholangiocarcinoma (CCA) is crucial for optimizing surgical decisions and patient outcomes.

• CCA shows significant heterogeneity, with distinct genomic profiles linked to tumor location—this may affect surgical approach.
• Intrahepatic CCAs frequently harbor targetable mutations like FGFR2 fusions and IDH1/2 mutations, offering new avenues for therapy.

Surgeons can enhance patient selection based on these molecular characteristics to improve treatment strategies and outcomes.

• The study highlights the need for a more precise classification system that aligns with biological characteristics, guiding surgical interventions and follow-up.