Aim: To evaluate and compare the appropriate effective dose of 131I therapy for successful ablation in differentiated thyroid cancer patients demonstrating multifocal radioiodine uptake/uptake outside thyroid bed and thus proposing this factor as an important determinant in justifying higher dose for successful radioiodine ablation in neck as compared to that administered for standard unifocal radioiodine uptake in neck after total thyroidectomyMaterials and Methods: Patients of differentiated carcinoma of thyroid (post- thyroidectomy and considered for radioiodine remnant ablative therapy) including aggressive histological variants were included in the study (n=125). A preablative scan with 3.7 MBq 131I, post-treatment scan before discharge and followup scan after 6 months of therapy with 0.111- 0.136 GBq 131I were part of regular protocol. Scans were done on gamma camera and interpreted by two independent Nuclear Medicine Physicians. In case of discordance, opinion of a third Nuclear Medicine Physician was taken. Patients with multifocal uptake in neck/uptake outside thyroid bed in preablative and/or post ablative scintigraphy were included in the study group (84/125). Unifocal uptake in neck in both preablative and postablative scintigraphy comprised the control group (41/125). Patients with distant metastasis were excluded. 49/84 patients with multifocal neck uptake received low ablative dose (1.85GBq) and 35/84 received high dose 3.7-7.4 GBq. 7/84 patient’s scan had discordant findings and were dropped in favor of multifocality restricted to thyroid bed. 20/41 patients with unifocal neck uptake in scintigraphy received low ablative dose (1.85GBq) and 21 received high ablative dose (3.7-7.4 GBq). The objective ablation parameters were Scintigraphy, biochemical markers (Thyroglobulin), relevant radiological investigations and SPECT-CT when available.Results: 44.44 % (20/45) of patients demonstrating multifocal uptake outside thyroid bed in pre/ post-treatment dose scan treated with initial low dose (1.85 GBq) required a second higher dose of radioiodine (total 3.7-7.4 GBq). 95% (19/20) had either papillary or its follicular variant as histopathology. 5% (1/20) had follicular carcinoma of thyroid. 100% (32/32) curative rate was noted in patients with multifocal uptake in and outside thyroid bed treated with initial higher radioiodine ablative dose. 2/32 patients had aggressive histopathology. 31.25% (10/32) of patients with multifocal uptake outside thyroid bed were missed on 3.7 MBq preablative scan.Conclusion: Multifocality outside thyroid bed in pre / post ablative scans required second high dose treatment in significant number of patients who were treated with low ablative radioiodine dose. The preablative diagnostic scan can play a major role in the risk stratification and dose determination.