Epithelial growth factor receptor (EGFR) appears as a key element in colorectal carcinogenesis. It displays high levels of expression. Its activation induces cell proliferation, angiogenesis, cell mobility and inhibition of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules tyrosine kinase inhibitors have been developed. For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats. Pathologists are involved in the selection of patients for a monoclonal antibody based targeted treatment, Erbitux (cetuximab), and numerous standardization efforts are provided. No consensus has been reached, to date, for a scoring system for immunohistochemistry. No correlation has been found so far between EGFR level of expression and response to cetuximab. Whether and how the EGFR status has to be tested for the selection of patients is a non answered question. The selection of the "right patient for the right treatment" might be through the evaluation of other putative markers involved in resistance. EGFR testing may be required before targeted treatment. An exciting endpoint might be the functional and dynamic evaluation of EGFR and downstream proteins for patients, before and during treatment.