INTRODUCTION: Radioiodine therapy for patients with differentiated thyroid cancer aims at reducing tumor recurrence by eradicating residual macro- and microscopic foci. Side effects are generally rare, tenuous and transient, with little clinical significance. OBJECTIVE: To report a rare case of differentiated thyroid carcinoma presenting a large expansive solid mass at the base of the skull, with invasion of the left masticatory muscle and adjacent subcutaneous tissue, and without invasion of the carotid space, which evolved to carotid artery rupture following radioiodine therapy. DISCUSSION: Side effects are uncommon after radioiodine therapy and when present, have mild intensity. Serious adverse events are very rare, especially those arising from structures not directly invaded by metastatic tissue with radioiodine uptake, as occurred in this case. This occurrence serves to raise awareness of the need for increased care when using radioiodine therapy on high-avidity masses located close to important structures.