A 70-year-old man was admitted to our hospital with an abnormal chest X-ray shadow. Bronchoscopy revealed an adenocarcinoma tumour with an epidermal growth factor receptor (EGFR) exon 19 deletion. Positron emission tomography-computed tomography scanning and magnetic resonance imaging showed advanced stage IV lung cancer. He was treated with erlotinib as a first-line drug, which maintained a clinical response for 16 months. After disease progression, a re-biopsy was done from the tumour in the right lower lobe. The obtained specimen harboured both small-cell lung cancer (SCLC) transformation with retention of the EGFR 19 deletion and the development of an EGFR T790M mutation. We came across a very rare condition of concomitant T790M mutation and SCLC transformation after acquired resistance to EGFR-tyrosine kinase inhibitor.