Herein, we quantified circulating exosomal ENTPD2 in patients with colon cancer and showed that ENTPD2 was more enriched in serum exosomes from colon cancer patients than in those from healthy controls and that a high abundance of ENTPD2 was closely associated with an advanced TNM stage and a high tumor invasion depth. The gene discussed is ENTPD2; the disease is colonic neoplasm.