The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion in Asian population than in whites. The prevalence of these mutations among Arab patients is unknown. The objective of this study was to report the frequency and spectrum of EGFR mutations in our population with lung adenocarcinoma, and the effect of this mutation on treatment outcome. Tumor specimens from 81 patients histological diagnosed as NSCLC adenocarcinoma were reviewed by our local pathologist and then sent to Lab 21 London, UK. Samples were tested for 28 mutations in EGFR gene. Positive patients received TKI and negative patients received chemotherapy. Data were collected and retrospectively analyzed to determine frequency and spectrum of EGFR positivity. Patients were followed for time to progression (TTP) and overall survival (OS). Overall frequency of EGFR mutation was 37%; Del 19 (46.6%), L858R (40%), D719x and insertion 20 (6.7%) for each. Females and nonsmokers exhibited a statistically significant higher EGFR positivity (P = 0.003, 0.059) respectively. Overall response rate (ORR) was 76.6% and 43% in EGFR positive and negative cases respectively (P = 0.002). There was a statistically significant difference in TTP and OS between EGFR positive and negative patients (P = 0.035 and 0.039 respectively). Arab patients exhibit an EGFR mutation pattern that is closer to Asian population. EGFR gene mutation subtypes are the same as that reported worldwide. A statistically significant TTP and OS benefit was noticed in EGFR positive patients compared to EGFR negative cases.