Background: Ultrasound reveals thyroid abnormalities in 18% of children and adolescents, of which, 22% are malignant. This creates a dilemma for practitioners who must distinguish lesions that require removal (high risk for malignancy) from lesions that can be observed (low risk for malignancy). Furthermore, treatment of children with differentiated thyroid cancer (DTC) is evolving. Previous treatments were based on adult protocols prescribing total thyroidectomy, lymph node dissection, and radioactive iodine (RAI) ablation for children with DTC, regardless of disease extent. This achieved excellent disease-free survival but high, and potentially avoidable, surgical and medical complications including an increase in secondary non-thyroid malignancies. Methods: This manuscript is a synopsis of cases presented during a symposium at the 2015 Pediatric Endocrine Society meeting (San Diego, CA) with recommendations based on the American Thyroid Association (ATA) management guidelines for children and adolescents with thyroid nodules and DTC. Results: The cases were selected to demonstrate application of the guidelines across a variety of pediatric patients with DTC highlighting key points of the ATA guidelines. The cases will assist practitioners in learning how to apply these guidelines to patient management. Conclusion: Treatment of children with thyroid nodules and DTC is evolving. Current guidelines emphasize the importance of surgery by experienced teams and deferral of RAI ablation for low-risk patients.