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Transformation to small cell lung cancer (SCLC) is one of the mechanisms of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it is uncertain how it works and there is no standard treatment after the transformation. In this study, 7 patients with transformation of SCLC from advanced lung adenocarcinoma (ADC) were analyzed retrospectively and the clinical pathology, imaging characteristics and treatment were analyzed.We identified 7 patients with primary lung ADC that showed transformation to SCLC on second biopsy during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were performed in initial biopsy samples.Seven patients showed transformation from ADC to SCLC, of which 6 patients were 19 del EGFR mutation, only 1 patient is L858R mutations. The imaging forms did not have the typical imaging features of primary SCLC. All patients underwent etoposide and carboplatin (EC) regimen chemotherapy after pathological transformation. However, the response rate of EC was less than primary small cell lung cancer. One of the patients was receiving EC for 4 cycles. After chemotherapy the patients performed radiation therapy and finally with erlotinib maintains treatment, the progress free survival (PFS) was more than 12 months.NSCLC can acquire a neuroendocrine phenotype with EGFR-TKI treatment. The transmutation is more common in 19del mutation patients. A comprehensive treatment based on EC regimen chemotherapy and the maintenance with EGFR-TKI is likely to be the appropriate treatment for these patients.