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Thyroid nodules are less frequent in childhood than in adulthood, but are more often malignant. Recent estimates suggest that up to 25% of thyroid nodules in children are malignant, therefore, a more aggressive approach is recommended. In this review, we suggest an approach based on a first-step clinical, laboratory, and sonographic evaluation. A history of irradiation of the neck, cranium or upper thorax, previous thyroid diseases or thyroid neoplasms in the family should alert clinicians as being associated with a greater likelihood of malignant nodules. Signs or symptoms of hyperthyroidism and dysmorphic features should be carefully considered during the physical examination. Palpable firm lymph nodes, found in some 70% of cases, are the most significant clinical finding in children with malignant nodules. Although the routine determination of calcitonin levels is not uniformly practiced, it can help recognize sporadic or familial medullary thyroid neoplasms. Blood thyroid stimulating hormone, free thyroxine, and free triiodothyronine determinations (the latter in case of symptoms of hyperthyroidism) are aimed at identifying the few hyperthyroid patients, for whom the next step should be scintiscan. Hyperthyroid patients usually disclose an increased uptake, and a diagnosis of toxic adenoma is commonly made. Cases with normal thyroid function or hypothyroidism (which is usually subclinical) should be evaluated by fine-needle aspiration biopsy (FNAB). In eu/hypo-thyroid patients, scintiscan provides poor diagnostic information and should not be routinely employed. Thyroid ultrasonography is used to select cases for FNAB. Although …