(131)I therapy is used in the treatment of differentiated thyroid cancer both to ablate the post-surgical thyroid remnant and to treat recurrent or metastatic cancer. The optimum administered activity for ablation remains controversial: the most commonly used method is the administration of a fixed radioiodine activity (1110-3700 MBq or more); an alternative is the administration of an activity individually calculated to deliver a prescribed absorbed dose (usually 300 Gy for remnant ablation and 80 Gy for treatment of metastasis). Neither of these two approaches is based on a theoretical model and for this reason the debate on the optimization of (131)I therapy of thyroid cancer could have a weak grounding. In this paper, the meaning of the fixed value of target absorbed dose (Gy) is discussed and a mathematical model for remnant/metastasis optimum absorbed dose calculation is presented. This model is based on the desired reduction of the volume of the target (remnant or metastasis) and allows one to calculate individually the value of the optimum target absorbed dose (Gy) and consequently the optimum therapeutic activity to administer to the patient.