ObjectiveTo improve the knowledge of erlotinib-induced severe rash and fatal interstitial lung disease (ILD). MethodsThe clinical feature and radiology of erlotinib-associated severe rash and fatal ILD were analyzed in one patient with advanced non-small cell lung cancer (NSCLC) in the 81st Hospital of Chinese PLA,and the related literatures were reviewed. ResultsThe patient was a 78-year-old male non-smoker with stage Ⅳ right lower lobe squamous cell carcinoma,and his epidermal growth factor receptor gene showed mutation at exon 21.He had a history of chronic obstructive pulmonary disease and mild pulmonary fibrosis.Following one cycle of chemotherapy with gemcitabine plus cisplatin,he received erlotinib 150 mg daily.After 40 days of targeting therapy,the size of the lung cancer was decreased significantly concomitant with severe rash.Again,severe rash and fatal ILD appeared after using erlotinib 100 mg daily for 4 days and 50 mg daily for 2 days,respectively.The tumor progressed markedly although both rash and ILD were almost abolished following withdrawal of erlotinib as well as empirical impact of glucocorticoid and sequential therapy. ConclusionPhysicians should be alerted to the possibility of erlotinib-induced severe rash and fatal ILD.Those with pathologic findings of usual interstitial pneumonia on resected lung specimens or known pulmonary fibrosis may be at particular risk for erlotinib-related pulmonary toxicity.