Thyroidectomy followed by administration of large activities of 131-iodine (131I) is the treatment of choice for differentiated thyroid carcinoma (DTC). The serum thyroglobulin (Tg) measurement during hypothyroidism (offT4-Tg), just before radioiodine thyroid ablation, has proved to be effective for predicting persistent/recurrent disease. However, the Tg measurement cannot be used as a corresponding value for preablative offT4-Tg when rhTSH is used as stimulous before treatment. The present study was undertaken to evaluate if post-thyroidectomy Tg values, measured before rhTSH-stimulation and radioiodine administration, is of prognostic value in patients affected by DTC. We enrolled 28 patients with DTC and submitted to total thyroidectomy. Thyroxine (T4) treatment was started just after surgery to suppress TSH levels. Six to nine weeks later Tg levels were measured both basally (onT4-Tg) and after rhTSH (rhTSH-Tg) stimulation. Subsequently, T4 was stopped and serum Tg measured (offT4-Tg) just before 3700 MBq of 131I-iodide administration. A post-treatment whole body scan (PT-WBS) was performed and neck radioiodine uptake (RAIU) measured. A significant relationship was found between onT4-Tg and both rhTSH-Tg and offT4-Tg. The onT4-Tg levels of 0.2 ng/mL or higher predicted PT-WBS results with a 100% negative and 43% positive predictive values, respectively. Additionally onT4-Tg levels of 0.9 ng/mL or more predicts 12-months recurrences with 100% negative and 60% positive predictive value. In comparison, 1.0 ng/mL or higher offT4-Tg values predicted PT-WBS results and 12-months restaging with 94% and 100% negative and 45% and 27% positive predictive value, respectively. Basing on our data we conclude that preablative onT4-Tg may be of value as prognostic marker when rhTSH-aided radioiodine ablation is done. Additionally, the role of preblative onT4-Tg measurement as a yard-stick for radioiodine ablation should be further evaluate.