Although endoscopy can be used to diagnose colorectal cancer early, however, due to its invasiveness and other limitations, most patients have advanced or even metastatic status at the time of diagnosis. The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab enriches the treatment of metastatic colorectal cancer, and its therapeutic effect is related to mutation in the KRAS gene. Therefore, it is necessary to detect the KRAS gene before use of an anti-EGFR monoclonal antibody. Extensive research on exosomes has led us to consider whether exosomes can be used to determine KRAS mutation status. This review focuses on the feasibility of using exosomes to detect KRAS mutations to guide the use of anti-EGFR monoclonal antibodies in patients with colorectal cancer.