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Background: Concerning the different clinical behavior of epidermal growth factor receptor (EGFR) subtypes in advanced-stage lung cancer patients, the current study aimed to evaluate the clinical, pathological, and prognostic significance of EGFR mutation subtypes, and treatment response in patients with advanced-stage lung cancer. Methods and results: A retrospective study enrolled a total of 346 patients with advanced-stage lung cancer tested for EGFR mutation. EGFR mutation was analyzed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Statistical analysis was performed using SPSS version 20.0. EGFR mutation was evident in 38% of patients with the highest prevalence of exon 19 deletions. A higher incidence of 19-deletions and 20-insertions were observed in young patients, while a higher incidence of L858R was noted in old age patients. Patients with de-novo T790M failed to improve their OS by any of the treatment modalities. Patients with de-novo T790M mutation have a higher risk of developing lung, liver, and multiple site metastases while patients with L858R mutation have a higher risk of developing brain metastasis. Additionally, patients with 19 deletion mutation did not improve their OS after receiving conventional chemotherapy hence, they demonstrate better survival only after EGFR-TKIs. Multivariate survival analysis predicted chemotherapy as an independent predictor of OS. Conclusion: Besides clinicopathological and prognostic consequences of EGFR mutation and mutation subtypes, patients harboring TKI sensitive, or insensitive mutations reveal different secondary disease development and hence should be treated accordingly for better survival. Current findings may provide the basis for a better treatment strategy. [ABSTRACT FROM AUTHOR]