There was tumor heterogeneity in small bronchoscopic biopsies and challenges in histological subtyping of poorly differentiated carcinomas, repeated responses to EGFR TKIs based on EGFR mutation (in spite of initial wild-type characterization), and acquired EGFR-TKI resistance through transformation to the high-grade neuroendocrine carcinoma spectrum. This evidence concerns the gene EGFR and neuroendocrine carcinoma.