The 21 trisomy (Down syndrome, DS) is one of the most common chromosomal disorders in pediatric practice. Thyroid dysfunctions in these patients are very common. Hypothyroidism is diagnosed in nearly 50% of patients in this population and the number of patients increases with age. Hyperthyroidism is much less frequently diagnosed in children with DS. Hyperthyroidism treatment strategy is highly important for an undisturbed and balanced development of the children. We report two children with Down syndrome and hyperthyroidism. The processes of treatment were significantly different.