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It is characterized by heterogeneous clinicopathological features as well as molecular landscapes. The updated World Health Organization (WHO) classification system underscores the critical distinction between small-duct and large-duct types, which exhibit distinct morphologic patterns, immunohistochemical profiles, molecular alterations, and clinical outcomes. Besides, rare and unique morphologic subtypes of iCCA continue to challenge diagnostic and treatment paradigms. This review provides an overview of the 2026 WHO classification and evolving concepts in iCCA, with a particular emphasis on the practical application of immunohistochemical and emerging molecular biomarkers essential for an accurate diagnosis and guiding targeted therapies. Furthermore, this manuscript addresses contemporary controversies and unresolved emerging practical issues with iCCA that are reshaping personalized therapeutic strategies and prognostication.<\/jats:p>","DOI":"10.1007\/s00428-026-04746-1","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:25:46Z","timestamp":1792722346000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrahepatic cholangiocarcinoma: contemporary classification, molecular pathology, and emerging concepts"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8251-902X","authenticated-orcid":false,"given":"Kwun Wah","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2526-4080","authenticated-orcid":false,"given":"Sanjay","family":"Kakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"4746_CR1","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/S1470-2045(20)30157-1","volume":"21","author":"GK Abou-Alfa","year":"2020","unstructured":"Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX (2020) Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3. study Lancet Oncol 21:796\u2013807. https:\/\/doi.org\/10.1016\/S1470-2045(20)30157-1","journal-title":"study Lancet Oncol"},{"key":"4746_CR2","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/S1470-2045(20)30109-1","volume":"21","author":"GK Abou-Alfa","year":"2020","unstructured":"Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, Paulson AS, Borad MJ, Gallinson D, Murphy AG, Oh DY, Dotan E, Catenacci DV, Van Cutsem E, Ji T, Lihou CF, Zhen H, Feliz L, Vogel A (2020) Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2. study Lancet Oncol 21:671\u2013684. https:\/\/doi.org\/10.1016\/S1470-2045(20)30109-1","journal-title":"study Lancet Oncol"},{"key":"4746_CR3","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/modpathol.2017.22","volume":"30","author":"M Akita","year":"2017","unstructured":"Akita M, Fujikura K, Ajiki T, Fukumoto T, Otani K, Azuma T, Itoh T, Ku Y, Zen Y (2017) Dichotomy in intrahepatic cholangiocarcinomas based on histologic similarities to hilar. cholangiocarcinomas Mod Pathol 30:986\u2013997. https:\/\/doi.org\/10.1038\/modpathol.2017.22","journal-title":"cholangiocarcinomas Mod Pathol"},{"key":"4746_CR4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.humpath.2020.12.005","volume":"109","author":"M Akita","year":"2021","unstructured":"Akita M, Sawada R, Komatsu M, Suleman N, Itoh T, Ajiki T, Heaton N, Fukumoto T, Zen Y (2021) An immunostaining panel of C-reactive protein, N-cadherin, and S100 calcium binding protein P is useful for intrahepatic cholangiocarcinoma subtyping. 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