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The incidence of appendiceal cancer (AC) is rising, particularly among individuals younger than 50 years (early-onset AC), with unexplained etiologies. The unique spectrum of somatic cancer gene variations among patients with early-onset AC is largely undetermined. To characterize the frequency of somatic variations and genomic patterns among patients with early-onset (age 50 years) vs late-onset (age ≥50 years) AC. This cohort study included individuals aged 18 years and older diagnosed with pathologically verified AC. Cases with cli