Epidermal growth factor receptor (EGFR) inhibitors are being used to treat several malignancies involving the head and neck, breast, lung, kidney, prostate, pancreas, and brain. EGFRs are overexpressed in malignancies and usually correlate with a poor prognosis, especially in patients with non–small cell lung cancer. Two categories of EGFR inhibitors are available: monoclonal antibodies and small receptor tyrosine kinase inhibitors. Abrupt onset of a cutaneous eruption is commonly seen in patients treated with these agents. This article discusses the significance of EGFRs, presents an illustrative case report with description of the characteristics of the cutaneous eruption associated with inhibiting agents, and assesses management of affected patients.