Introduction Patients with unresectable non-small cell lung cancer (NSCLC) may benefit from chemotherapy, tyrosine kinase inhibitor (TKI) therapy, or both. TKI therapy may be administered to the subset of patients who harbor the epidermal growth factor receptor (EGFR) mutation. EGFR mutation testing now plays a vital role in the diagnostic work-up of advanced NSCLC patients to determine which patients are more likely to benefit from TKI therapy. The role of surgery in these patients is mostly limited to obtaining an adequate biopsy for histological, immunohistochemical, and EGFR analysis using the least invasive methods possible. It is thought that larger volume samples, such as those obtained from traditional surgical lung biopsies (SLBs), have better yield than small volume samples, such as those obtained from transthoracic needle lung biopsies (ITNLBs), for EGFR analysis. Aim The aim of this was to determine which biopsy procedures provide superior yield for EGFR mutation analysis among primary NSCLC patients at the Eric Williams Medical Sciences Complex (EWMSC) and whether these tissue yields are in keeping with international recommendations. Methods This is a retrospective, observational study using patient data obtained from the Lung Malignancy Unit, which is based at the EWMSC. The study population was limited to primary NSCLC patients presenting to the EWMSC from January 2014 to June 2017 whose biopsy samples were sent for EGFR testing. Relevant patient data were entered onto a spreadsheet using Microsoft Excel. Patients were classified as having had either an SLB, bronchial biopsy (BB), TTNLB, or some other biopsy procedure. All samples were sent for histological analysis, followed by immunohistochemistry and finally EGFR testing. All EGFR mutation analysis was performed at a single laboratory in the USA. A minimum of 200 tumor cells or 10% tumor content defined an adequate sample for EGFR mutation analysis. Samples that yielded a positive or negative result were considered adequate samples in this study. The number of adequate and inadequate samples for each procedure group was tabulated and the yield was determined as the percentage of adequate samples obtained for each procedure group. Results SLBs had superior yield (95.6%) compared to BBs (88.5%) and TTNLB (85%) in obtaining adequate samples for EGFR analysis. Conclusion SLBs demonstrated superior yield in attaining adequate tissue samples for EGFR mutation analysis compared to BBs and TTNLBs.