Objective Combined small cell lung cancer (CSCLC) is currently considered a subset of SCLC and have been reported to account for less than 1-3.2% of all SCLCs.Accurate understanding of CSCLCs is of great importance because treatment strategies are significantly different for NSCLC and SCLC.To address molecular features of different components in CSCLC we analyzed mutation status in CSCLC tumor samples in EGFR signal pathway.Methods Seven CSCLC samples were included in direct sequencing for mutation analysis of EGFR, KRAS, PIK3CA, BRAF, and PTEN.Results Mutations were detected in 4 of 7 (57.1%) CSCLC patients.EGFR Exon 18 mutations were identified in two patients among whom the mutation was identified in both adenocarcinoma component and SCLC combined adenocarcinoma component of one patient.The similar situation also happened in another one with PTEN C511T mutations both conventional SCLC component and SCLC combined adenocarcinoma component.Both KRAS and PIK3CA were detected in one SCLC combined adenocarcinoma patient and no mutation in BRAF was identified.Conclusion Our result is consistent with previous work that the individual components of CSCLC are closely related, despite their distinct morphologic appearances.