Background: Thyroid cancer is the most prevalent
endocrine malignancy. Based on the increased understanding of thyroid tumourigenesis, novel
therapeutic agents have been identified. However, given
the low incidence, the good prognosis of the majority of these tumours and the limited evidence of different
treatment modalities, a wide variety of treatment strategies are available. These are mostly based on small studies, data from retrospective analyses and the particular experiences of treating physicians. We discuss the recent developments in the treatment of advanced differentiated thyroid cancer. Case description: Three cases demonstrate the considerations involved in treatment decisions for patients with advanced thyroid cancer. The first patient achieved stable disease for over five years with different targeted therapies. The second patient shows the potential (severe) toxicity of these drugs and the third patient illustrates the indolent nature of this disease. Conclusion: The treatment of patients with extensively metastasised thyroid cancer is very complicated. The timing of initiation of therapy and the potential toxicity of targeted therapies are important in the clinical decision to treat or not to treat because of the slowly progressive course of differentiated thyroid cancer. When targeted therapy is considered, it remains of great importance to enrol patients in clinical studies in order to further determine the position of these therapies, to develop more effective (combination) treatment schemes, and above all, to identify those patients that truly benefit.