Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers includinglung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosinekinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks(FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls.The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performedusing PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations weredetected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients,exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patientswith EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs andhave responded well to therapy over the last 15 months. The control patients had no mutations in any of theexons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patientsdiagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and itsrole as an important predictive marker for response to oral TKI in the south Indian population.