This consensus statement, conceived as a joint initiative of the Spanish Society of Pathology and the Spanish Society of Medical Oncology, makes diagnostic and treatment recommendations for the management of patients with hereditary, localised and advanced CRC based on the current scientific evidence on biomarker use. This consensus statement thus provides an opportunity to improve healthcare efficiency and resource use, which will benefit these patients. Based on the currently available data on this subject, this expert group recommends testing for microsatellite instability (MSI) in patients with localised CRC, as this is a strong predictive factor for deciding on adjuvant treatment. However, although the ColoPrint(®) and Oncotype Dx(®) gene expression signatures have been shown to have prognostic value, no consensus yet exists concerning their use in clinical practice. For advanced CRC, it is essential to test for KRAS mutation status before administering an anti-EGFR treatment, such as cetuximab or panitumumab. However, testing for other biomarkers, such as BRAF, EGFR, PI3K and PTEN mutations, should not be done routinely, because this does not influence treatment planning at the present time. Other important issues addressed include organisational requirements and the quality controls needed for proper testing of these biomarkers as well as the legal implications to be borne in mind when testing some biomarkers.