Squamous cell carcinoma of the penis is rare in daily practice. Epidermal growth factor receptor is widely overexpressed in this type of cancer. In a metastatic situation, chemotherapy has modest efficacy. Agents targeting this receptor, including Cetuximab, are effective as monotherapy or in combination with chemotherapy. The finding was fortuitous in the anatomopathological analysis of a resection specimen for phimosis. It progressed first to the inguinal lymph nodes 3 months after surgery and then rapidly to the lungs and liver after the first line of chemotherapy. Cetuximab monotherapy in the second line of therapy was well tolerated and showed a complete response after 6 months of treatment. This response has been maintained for 5 years of treatment. The efficacy of agents targeting the Epidermal Growth Factor Receptor in squamous cell carcinoma of the penis opens the way to therapeutic optimization.