EGF receptor (EGFR) represents an attractive target for anticancer therapies in a variety of malignant neoplasms, including colorectal, non-small-cell lung, head and neck carcinomas and gliomas. Monoclonal antibodies, such as cetuximab, are directed against the extracellular EGFR domain, whereas small molecules are targeting the intracellular tyrosine kinase domain. Particularly for application of drugs against extracellular EGFR parts, knowledge about EGFR levels within the cell membrane is of high import, because only EGFR-depending tumors respond to these therapeutic approaches. Immunohistochemical investigation of tissue slides of the primary tumor are performed to screen for EGFR occurrence in tumor cells. Since 2004, the combination of 'EGFR PharmDx kit', a diagnostic test for EGFR, and subsequent application of cetuximab in EGFR-positive colon carcinomas has been approved by the US FDA. It represents the second approved combination of diagnostic tools and dependent application of monoclonal antibody therapies after the successful HercepTest/Herceptin for breast carcinomas. This proceeding represents an important step toward a personalized cancer therapy with major advantages for patients, mainly reduction of toxic side effects and dramatically increased efficiency.