© 2022 College of Physicians and Surgeons Pakistan. All rights reserved.Objective: To compare the detection of transthoracic tru-cut biopsy performed on metabolically active areas in positron emission tomography (PET) for the diagnosis of lung cancer, compared to only CT scan-guided biopsy. Study Design: Descriptive study. Place and Duration of Study: Department of Thoracic Surgery, Kayseri City Training and Research Hospital, Turkey, between December 2020 to June 2021. Methodology: Patients of suspected lung cancer with pre-transthoracic biopsy chest computerised tomography and without positron emission tomography were included in Group A; while, patients with both and positron emission tomography chest computerised tomography were included in Group B. Based on the CT findings of the patients in Group A, a biopsy was obtained from the most appropriate place. The patients in Group B were evaluated by a nuclear medicine specialist and the place with the highest maximum standardised uptake value before the biopsy was marked and the area to be biopsied was determined. Results: The malignancy detection rate was significantly higher in Group B (48/50 patients, 96%) than in Group A (36/50 patients, 72%, p=0.001). Two lesions in the Group B (4 %) and 14 lesions in the Group A (28 %) were found to give benign results (p=0.001). Biopsy was repeated in one patient of Group B, and in five patients of Group A due to an initial negative diagnosis. The sensitivity of PET/CT in predicting malignant tumor was 96%, with the positive predictive value (PPV) of 98.0%; while the sensitivity of CT was 74.5%, with PPV of 82%. Conclusion: Transthoracic biopsies taken by considering metabolically active areas of the mass in positron emission tomography-guided can both increase diagnosis rate and reduce the complication rate by preventing repeated biopsies.