Background: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated genomic alteration in adolescent and young adult (AYA)-onset sporadic CRC patients who aged between 15 and 39 years. Methods: DNA from 90 archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically confirmed adenocarcinoma with proficient mismatch repair tumors at Siriraj Hospital (Bangkok, Thailand) were extracted. Patients who clinically suspected familial adenomatous polyposis were excluded. Gene mutational analysis was performed by next-generation sequencing (NGS) using an Oncomine Comprehensive Assay Plus kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA) and compared with previous reported molecular data in adult-onset CRC from our group. Results: The top 5 mutations frequency observed were TP53, KRAS, FBXW7, PIK3CA, and SMAD4 mutations which were comparable to what reported in adult-onset CRC. However, FBXW7, PIK3CA, NOTCH1, FGFR3, ERBB2, and PTEN were reported more frequent in AYA group. No difference in number of KRAS, NRAS, and BRAF mutations among 2 groups. Table below shows key cancer genes mutation frequencies. Conclusions: This study is the comprehensive report hotspot mutations using NGS in sporadic AYA-onset sporadic CRC patients. The most commonly identified gene mutation frequencies among AYA-onset were similar to those reported in adult-onset, except for FBXW7, PIK3CA, NOTCH1, FGFR3, ERBB2, and PTEN mutations that had a slightly higher frequency. Further studies on larger sample set for genetic and epigenetic landscape are required.