The objective of this work was to evaluate the diagnosis and management of patients with substernal goiter (SSG) on the basis of our experience. We conducted a retrospective study of all SSGs within a series of 591 thyroidectomies performed in a tertiary referral center over a period of 14 years, analyzing epidemiological data, diagnostic criteria, and surgical results. There were 37 (6%) patients with descending goiter: 28 women (mean age 57.1 years) and 9 men (mean age 61 years). All 37 patients underwent successful surgical treatment without any major postoperative complications. A postoperative histological examination revealed a 16.6% incidence of malignancy. Despite the size and close proximity to vital organs in the mediastinum, all of the SSGs were managed successfully. A neck approach was used in all except for one patient who was operated on via sternotomy. A thorough preoperative evaluation including computed tomography scan of the neck and mediastinum, and an appropriate surgical technique ensure a positive outcome for most patients with an SSG.