Cholangiocarcinoma (CCA) is a type of hepatobiliary cancer that arises from cholangiocytes and is classified into intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) subtypes. These subtypes differ in location, epidemiology, etiology, pathogenesis, and treatment. iCCA incidence has increased over the past 30 years, with poor prognosis and low survival rates. CCA incidence varies geographically, influenced by risk factors such as infection with hepatobiliary flukes, hepatolithiasis, and primary sclerosing cholangitis (PSC). Genetic and epigenetic alterations, along with inflammatory signaling pathways, contribute to CCA development. CCA is surrounded by a dense stroma containing cancer-associated fibroblasts, which promote progression. Advanced imaging and cytologic techniques have improved detection of CCA subtypes. Surgical resection is the only curative treatment for early-stage disease, while liver transplantation following neoadjuvant chemoradiation is an option for some pCCAs. Recent studies have enhanced understanding of CCA epidemiology, pathogenesis, and treatment. Risk factors include hepatitis B and C viruses, cirrhosis, and inflammatory bowel disease. CCA development is associated with multiple cell types, including biliary epithelial cells, hepatocytes, and progenitor cells. Inflammation, cytokines, and growth factors contribute to CCA pathogenesis. Genetic mutations in oncogenes and tumor suppressor genes, such as TP53, KRAS, and IDH, are common in CCA. Epigenetic changes, including promoter hypermethylation and microRNA dysregulation, also play a role. The tumor microenvironment, including stromal cells and fibroblasts, supports CCA progression. Animal models are essential for developing new therapies. Diagnosis requires a high index of suspicion and a multidisciplinary approach. Treatment options include surgery, liver transplantation, and chemotherapy. Early detection improves prognosis, but CCA is often diagnosed at an advanced stage. Future research aims to identify genetic and molecular targets for personalized therapies. CCA remains a challenging disease with limited treatment options and poor survival rates.Cholangiocarcinoma (CCA) is a type of hepatobiliary cancer that arises from cholangiocytes and is classified into intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) subtypes. These subtypes differ in location, epidemiology, etiology, pathogenesis, and treatment. iCCA incidence has increased over the past 30 years, with poor prognosis and low survival rates. CCA incidence varies geographically, influenced by risk factors such as infection with hepatobiliary flukes, hepatolithiasis, and primary sclerosing cholangitis (PSC). Genetic and epigenetic alterations, along with inflammatory signaling pathways, contribute to CCA development. CCA is surrounded by a dense stroma containing cancer-associated fibroblasts, which promote progression. Advanced imaging and cytologic techniques have improved detection of CCA subtypes. Surgical resection is the only curative treatment for early-stage disease, while liver transplantation following neoadjuvant chemoradiation is an option for some pCCAs. Recent studies have enhanced understanding of CCA epidemiology, pathogenesis, and treatment. Risk factors include hepatitis B and C viruses, cirrhosis, and inflammatory bowel disease. CCA development is associated with multiple cell types, including biliary epithelial cells, hepatocytes, and progenitor cells. Inflammation, cytokines, and growth factors contribute to CCA pathogenesis. Genetic mutations in oncogenes and tumor suppressor genes, such as TP53, KRAS, and IDH, are common in CCA. Epigenetic changes, including promoter hypermethylation and microRNA dysregulation, also play a role. The tumor microenvironment, including stromal cells and fibroblasts, supports CCA progression. Animal models are essential for developing new therapies. Diagnosis requires a high index of suspicion and a multidisciplinary approach. Treatment options include surgery, liver transplantation, and chemotherapy. Early detection improves prognosis, but CCA is often diagnosed at an advanced stage. Future research aims to identify genetic and molecular targets for personalized therapies. CCA remains a challenging disease with limited treatment options and poor survival rates.