From Histology to Multi-Omics: Review of Chordoma Classification and Its Clinical Implications.

Chordoma is a rare malignant neoplasm of the axial skeleton, arising from notochordal remnants. No approved systemic therapies exist, and the 10-year overall survival is below 60%. Accurate molecular and pathological classification is a prerequisite for improved prognostication and the identification of actionable therapeutic targets; however, molecular classification of chordoma remains significantly less advanced than that of other neoplasms. This narrative review synthesizes proposed classification frameworks for chordoma across histological, radiological, surgical, genomic, epigenomic, transcriptomic, and proteomic domains. PubMed and CENTRAL were searched on 1 February 2026 using five queries: 'chordoma classification', 'chordoma DNA sequencing', 'chordoma RNA sequencing', 'chordoma methylation', and 'chordoma copy number'. Original research articles describing more than one patient and reporting a classification or subtyping framework were included; review articles, case reports, and non-English publications were excluded. Sample size and the use of a validation dataset were identified for each study. Results were synthesized qualitatively. A total of 108 studies encompassing 6349 individuals were included. Across six domains, four cross-cutting themes with prognostic and potential theranostic value emerged: copy number alterations, particularly