The biological agent cetuximab specifically inhibits the epidermal growth factor receptor (EGFR) function. Cetuximab is licensed for treatment of metastatic colorectal carcinoma, as it enhances the efficacy of cytostatic therapy. Acneiform drug eruptions are common side effects. We report two patients with metastatic colorectal carcinoma, who developed a severe acneiform drug eruption on the face and upper part of the body during the treatment with cetuximab. Triple therapy consisting of systemic isotretinoin, topical nadifloxacin and topical corticosteroid produced rapid improvement with moderate cheilitis the only side effect. We conclude that triple therapy is an effective treatment for patients with severe acneiform drug eruptions caused by cetuximab.