Mutations of the epidermal growth factor receptor (EGFR) gene have been reported 
in non-small-cell lung cancer (NSCLC), especially in patients with 
adenocarcinoma and never smokers. Some common somatic mutations in EGFR, 
including deletion mutations in exon 19 and leucine-to-arginine substitution at 
amino acid position 858 (L858R) in exon 21, have been examined for their ability 
to predict sensitivity to gefitinib or erlotinib, which are selective EGFR 
tyrosine kinase inhibitors (EGFR-TKIs). On the other hand, reports have shown 
that the threonine-to-methionine substitution at amino acid position 790 (T790M) 
in exon 20 is related to gefitinib resistance. Some studies have indicated that 
high copy numbers of the EGFR gene may be a more effective molecular predictor 
to responsiveness and prolonged survival in patients treated with EGFR-TKIs. 
Here, we describe two NSCLC patients with the L858R mutation who did not respond 
to gefitinib. Case 1 harbored both the T790M and L858R mutations, and 
fluorescence in situ hybridization showed EGFR gene amplification. Case 2 
harbored both the L858R and aspartic acid-to-tyrosine substitution at amino acid 
position 761 in exon 19 of EGFR mutations and had a high polysomy status for 
EGFR. In these two cases, tumors showed resistance to gefitinib treatment 
despite the presence of EGFR L858R mutation and increased copy number. Our 
findings encourage further molecular analysis to elucidate the relationship 
between the EGFR status, including mutations and amplifications, and the 
responsiveness of NSCLC to gefitinib.