Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared to late onset CRC (LOCRC). Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study is to develop a circulating miRNA signature for the diagnosis of patients with EOCRC.