A relatively newer class of chemotherapy agents, known as the epidermal growth factor receptor inhibitors (EGF-RIs), is being used to treat advanced stages of solid tumors. Acneiform eruptions are a frequent adverse effect and one which has been associated with increased survival in some studies. We describe 3 patients who presented shortly after initiation of EGF-RI therapy. Characteristics included an absence of comedones, facial and truncal involvement, and a perifollicular lymphoneutrophilic infiltrate detected on biopsy. Lesion counts were reduced with topical adapalene and oral tetracyclines in two patients. Patient 3 had dramatic clearance with low-dose isotretinoin (20 mg daily) until completion of EGF-RI therapy. Acneiform eruptions are a common adverse reaction to EGF-RI therapy and can be treated with traditional acne therapy. This should not be considered a drug hypersensitivity eruption or allergy, and patients should continue therapy. For patients with severe eruptions, oral isotretinoin is a consideration.