To figure out the relationship between the tumor marker clearance rate during the treatment period and the disease prognosis. Carcinoembryonic antigen (CEA) is a glycoprotein that has been widely used as a tumor marker in colorectal cancer for more than 30 years. This study evaluated the role of the CEA clearance rate during treatment and determined its relationship with chemotherapy regimens, increased metastasectomy rate, and overall survival. The medical records of 442 metastatic colorectal cancer patients whose primary tumors were treated with surgery followed by systemic therapy at a single center from 2000 to 2012 were reviewed. The CEA clearance rate was calculated as a change in CEA after 6 courses of therapy divided by the treatment period [(posttherapy CEA – pretherapy CEA)/days between therapy], and classified into 4 groups for further evaluation. The CEA clearance rate during treatment of stage IV colorectal cancer was significantly correlated with different chemotherapy regimens (P, 0.01); pretreatment CEA level (P, 0.01); tumor differentiation (P, 0.01); increased metastasectomy rate (P ¼ .02); and overall survival (P, 0.01). The CEA clearance rate during systemic therapy could evaluate patient treatment responses more precisely than traditionally rising or falling CEA levels, and may predict disease prognosis.