AbstractBackgroundNon‐small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with smoking being a critical risk factor. The identification of NSCLC patients harboring epidermal growth factor receptor (EGFR) mutations, sensitized to tyrosine kinase inhibitors, has revolutionized treatment plans, resulting in improved clinical responses and reduced chemotherapy toxicity. This study aimed to assess the relationship between EGFR mutations and smoking patterns in patients diagnosed with lung adenocarcinoma referred to major pathologic laboratories.MethodsThis cross‐sectional study included 217 NSCLC patients aged above 18 years. Molecular abnormalities of the EGFR gene were analyzed by polymerase chain reaction amplification of exons 18–21 accompanied by Sanger sequencing. Then, the data were analyzed using the SPSS 26 software. Logistic regression analysis,χ2test, and Mann–WhitneyUtest were used to evaluate the relation between EGFR mutations and smoking patterns.ResultsEGFR mutations were identified in 25.3% of patients, predominantly involving deletion in exon 19 (61.8%). For most of the mutant EGFR patients, the majority were nonsmokers (81.8%), and 52.7% were female patients. Besides, the median duration of smoking was 26 years and the median frequency of smoking was 23 pack‐years in the mutant EGFR group, both of which were lower compared to the wild mutant group. Moreover, female gender, current, and heavy smoking were significantly correlated with EGFR mutations based on the univariate logistic regression analysis (p: 0.004, 0.005, and 0.001, respectively).ConclusionsFemale gender and nonsmoker status were strongly associated with positive EGFR mutations. While guidelines traditionally recommended EGFR testing primarily for female nonsmokers with advanced NSCLC, our study in line with the recently published evidence has shown a significant prevalence of positive EGFR mutations among male patients and smokers. Therefore, routine mutation testing is suggested for all NSCLC patients. Considering the limited access to EGFR testing laboratories in developing countries, the results of such epidemiological surveys can assist oncologists in choosing the most suitable treatment plan.