Objective: Spontaneous thyroid gland hemorrhage is a rare event. The present retrospective study considered its clinical impact and management in a referral center. Methods: Clinical records of adult patients accessed in the last 10 years (2009-2018) in the Emergency Department of Policlinico Gemelli IRCCS were reviewed to study patients with spontaneous thyroid nodule hemorrhage. All demographic and radiologic or surgical parameters were included, with special attention to the characteristics of thyroid disease and clinical management. Results: Among the 631,129 adults who were registered during the period considered, 59 consecutive patients were included in the study. The mean age was 48.3 ± 14.3 years, with a prevalence of females. The main symptoms were acute neck pain, dyspnea, and dysphagia. All patients underwent ultrasound evaluation; computed tomography scan was performed on only 3 patients, finding one case of active intranodular bleeding requiring urgent surgery. Six patients required hospitalization; the others were discharged and referred for ambulatory endocrinology follow-up. Among them, 7 patients underwent surgery in the next 6 months, with malignant disease found in 3 cases (5.1%). Conclusion: Intrathyroidal spontaneous hemorrhage is a rare event, occurring in multinodular as well as in single-nodule thyroid disease. Although the clinical course is mostly benign, this condition should be carefully evaluated as, in rare circumstances, active bleeding could induce airway obstruction with the need for emergency surgery. Patients should be referred to endocrinology ambulatory follow-up because bleeding could arise as the first sign of malignant lesions in some cases. Abbreviations: CT = computed tomography; ED = emergency department; FNA = fine-needle aspiration; US = ultrasound.