Organ transplant recipients are at increased risk for aggressive cutaneous squamous cell carcinomas (cSCC) that recur and metastasize despite treatment with surgery, radiation, or both. Therapies targeting the epidermal growth factor receptor (EGFR) are being explored as treatments for metastatic cSCC. We describe our experience with two single-lung transplant patients who developed metastatic cSCC; failed surgical resection, radiation or chemoradiation therapy; and were ultimately treated with an EGFR inhibitor, cetuximab. Both patients died shortly after initiation of cetuximab due to diffuse alveolar damage, suggesting that EGFR inhibitors should be used with extreme caution in lung transplant recipients. © 2007 International Society for Heart and Lung Transplantation.