Epidermal growth factor receptor () mutations have emerged as the most well-studied oncogenic alterations in advanced non-small cell lung cancer. The presence of single common or rare mutations and extra complex mutations correlates with the response sensitivity to tyrosine kinase inhibitors. Therefore, given the lack of evidence for the emergence of rare mutation types, the pathogenic mechanisms of uncommon mutations and the optimal treatment strategies remain to be explored further. The present study describes the case of a patient diagnosed with lung adenocarcinoma (LUAD) carrying two rare exon 18 indel/G719C and exon 19 L747S mutations, in which persistent lesion shrinkage was exhibited within 16 months of osimertinib treatment. Given the paucity of clinical trials for the treatment of LUAD harboring complex mutations, the present detailed case description may provide clinicians with effective clinical experience in treating patients.