Purpose: Failure to gefitinib is generally believed to be associated with cross-resistance to other epidermal. growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Here we report a case whose active EGFR-mutant NSCLC responded to erlotinib treatment. Patient and methods: Lung specimen was obtained during diagnostic procedures from a 41-year-old Taiwanese mate smoker with adenocarcinoma. He received cisplatin-based chemotherapy following craniotomy to remove his brain metastasis. Tumor progressed in both lung and left adrenal gland. He underwent second-tine docetaxel chemotherapy. Tumor progressed again 7 months later. He was subsequently treated with gefitinib 250mg QD. Complete regression of the lung tumor and partial response of the left adrenal gland mass was achieved. Nine months later, the left lower lobe lung tumor and left adrenal gland tumor progressed. A tung biopsy from the left tower lobe disclosed an adenocarcinoma which harbored an in-frame deletion in exon 19 (heterozygous delE746-A750) of EGFR without a second mutation such as T790M in exon 20. Subsequent erlotinib 150 mg QD was administered. He experienced grade 1 skin rash, diarrhea and paronychia following erlotinib. Results: This patient achieved a partial response to erlotinib treatment. He remained on erlotinib for a total of 18 months until the left adrenal gland tumor progressed. Conclusions: This case demonstrated that NSCLC bearing in-frame deletion in exon 19 of EGFR may respond to erlotinib treatment following gefitinib failure. (c) 2007 Elsevier Ireland Ltd. All rights reserved.