Carcinoembryonic Antigen (CEA) and CA 19-9 are tumor markers expressed by colorectal cancers (CR), particularly in advanced cases. The aim of this study was to evaluate the prognostic value of pre-operative elevated CEA and/or CA 19-9 levels for patients with CR. Blood samples were collected from 74 patients. CEA and CA 19-9 were determined by ELISA (normal range: 0-3 ng/ml for CEA and 0-37 U/ml for CA 19-9). All patients were followed-up for at least 30 months or until death. At the time of diagnosis, 42% of the patients had elevated serum levels of CEA and 35% of CA 19-9. Relapse was observed in 33 patients, 73% of whom had elevated CEA and/or CA 19-9 levels. Among patients without relapse, 68% and 73% had normal values of CEA and CA 19-9, respectively. Ninety-three percent of patients, who had CR recurrence during the first year, had an elevated CEA and/or CA 19-9 level, while 67% of the patients with CR after 1 year, had normal tumor markers. Elevated pre-operative serum CEA and CA 19-9 levels were each predictive of increased cancer mortality (p = 0.001 for CEA, p = 0.01 for CA 19-9). Raised CEA and CA 19-9 levels identify patients at high risk for CR and death and may be useful in selecting patients for adjuvant therapy.