Two patients receiving epidermal growth factor receptor inhibitors for cancer treatment developed papulopustular eruptions a few days after starting treatment. One patient is a 56-year-old man with metastatic lung cancer treated with erlotinib. Bacterial cultures of the nares and a pustule showed no growth. The eruption improved with a lowered dose of erlotinib and the application of topical clindamycin solution and triamcinolone cream. The other patient is a 53-year-old man with metastatic rectal cancer treated with cetuximab. Bacterial culture of a pustule grew Staphylococcus aureus, and a skin biopsy specimen showed a suppurative folliculitis. The eruption improved with a two-week course of oral antibiotics and the application of topical clindamycin solution and triamcinolone cream. A papulopustular eruption occurs in up to 90% of patients treated with epidermal growth factor receptor blocking agents and may correlate with a positive response to chemotherapy. Treatment options are based on anecdotal evidence and may include topical antibiotics, topical glucocorticoids, and oral antibiotics for secondary infection.