Thyroid nodules are abnormal growths of tissue within the thyroid gland, with traditional treatment options including watchful waiting, hormone therapy, radioactive iodine, or surgical removal. Today, with the advent of minimally invasive percutaneous treatments, it is possible to reduce nodules volume using thermal (laser, radiofrequency, and cryoablation) or ultrasonic (HIFU) techniques. These procedures aim to offer an alternative to traditional surgery. However, treating giant nodules and goiters with retrojugular and substernal attitude can be challenging due to anatomical structures in the lower neck. Surgical or percutaneous ablation planning for substernal goiters requires a prior computed tomography (CT) scan to assess the correct anatomical relationships with the neck and mediastinal structures. Regarding the iceberg technique it must be considered that, although it provides good results in a significant percentage of patients, it involves a significant increase in costs (ablation scheduled in two different stages with the consequent need to use two different ablation needles). Minimally invasive percutaneous ablation and related ultrasound-guided ablation technologies should be considered a safe and valuable treatment options for thyroid nodules, also in challenging conditions such as substernal goiters.