Objective The aim of this study was to define a cutoff serum thyroglobulin (Tg) level associated with either residual or metastasis that may help decide postoperative radioactive iodine (RAI) scan and treatment in differentiated thyroid cancer (DTC) patients residing in low-income countries like Nepal. Methods We prospectively studied a total of 81 patients (female-to-male ratio of 3.0:1; mean age: 37.3 ± 14.0 years, within age range of 14-88 years) who underwent total thyroidectomy with/without neck dissection and were referred for RAI whole-body scan (WBS) ± RAI ablation or adjuvant treatment in the department of Nuclear Medicine, Chitwan Medical College. We calculated the cutoff value of Tg using receiver operating characteristic (ROC) curve analysis. Results Forty-six of 81 patients (56.7%) had remnants in the thyroid bed, 26/81 (32.1%) had regional lymph node metastasis, 9/81 (11.1%) had distant lymph node metastasis, 3/81 (3.7%) had lung metastases, and only 1/81 (1.2%) had bone metastases. RAI WBS was positive in 61/81 (75.3%) patients and negative in 20/81 (24.7%) patients. Seventeen of 81 (20.9%) patients had negative RAI scans with low serum Tg levels; only 3/81 (3.7%) patients had Tg elevated negative RAI scan (TENIS). Although scan was positive in 61/81 (75.3%) patients, 64/81 (79.0%) patients received treatment with RAI, of which 3/81 (3.7%) patients were TENIS patients. There was a significant difference in serum Tg levels between patients who received or did not receive RAI ablation or treatment ( p < 0.05). On ROC curve analysis, the cutoff value of Tg levels between patients who received and did not receive treatment was 2.9 ng/mL (sensitivity: 85.9%; specificity: 94.1%; positive predictive value [PPV], 98.2%; negative predictive value [NPV]: 64.0%; AUC: 0.938). Conclusion We identified a cutoff value of 2.9 ng/mL between patients who required or did not require treatment with high sensitivity, specificity, and PPVs.