BACKGROUND: The incidence of gastrointestinal stromal tumors (GISTs) has risen, but early-onset GISTs (age <
50 years) remain underexplored. This study aims to compare the clinical characteristics and prognostic outcomes of early-onset GISTs with later-onset cases (age ≥50 years). METHODS: We conducted a retrospective study using data on GISTs diagnosed from 2000 to 2021 in the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors for overall survival (OS) and cancer-specific survival (CSS) were analyzed using Cox regression and competing risk analysis. Kaplan-Meier and cumulative risk curves assessed survival disparities, and forest plots were used for subgroup analyses. Bias was minimized through multiple imputation, propensity score matching (PSM), and stratified regression. RESULTS: Among 12,608 GIST cases, 2,271 (18%) were early-onset, and 10,337 (82%) were later-onset. Median age and survival for early-onset cases were 43 years and 70 months, respectively, CONCLUSIONS: Early-onset GISTs have distinct clinicopathological features and better OS and CSS compared to later-onset patients.