Colorectal cancer (CRC) is the World's third most common cancer. Its prognosis is closely related to the disease stage at the time of diagnosis. Here we review the role of clinical biomarkers (tissue, serum, and faecal) in the management of CRC. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic. In the next future the hope is to have a complete panel of clinical biomarkers to use in every setting of CRC disease, and at the same time: 1) to receive information about prognostic significance by their expression and 2) to be oriented in the choice of the adequate treatment.