• Cholangiocarcinomas show significant biological diversity, influencing treatment and patient selection.
• High rates of actionable mutations in intrahepatic cholangiocarcinoma, such as FGFR2 fusions and IDH1/2 mutations, offer new therapeutic targets.
• Understanding the molecular subtypes can enhance surgical approaches and refine prognostic assessments.

Tailoring surgical strategies based on molecular profiles can improve outcomes in cholangiocarcinoma patients.