The development of targeted antitumor agent aiming the HER family of tyrosine kinase transmembrane receptors, focused on the issue of target detection. For HER2, the techniques used to detect an overexpression are well established and none has, to date, shown its superiority. These are immunohistochemistry (protein) and in situ fluorescent hybridization (DNA). For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats. Immunohistochemistry appears to be the most appropriate test for clinical use but standardized assays and scoring systems are mandatory. The EGFR levels of expression are very high in some normal tissues such as oral mucosae. In tumors, EGFR levels are variable. The highest expression is found in head and neck epithelial tumors. EGFR expression is also elevated in oral and lung dysplasia. EGFR testing may be required before targeted treatment. An exciting endpoint would be the functional and dynamic evaluation of EGFR and downstream proteins for patients, before and during treatment.