The authors report a 54-year-old woman with papillary thyroid carcinoma (Lindsay type, pT2 N0 M1) with pulmonary metastases. After a total thyroidectomy, a series of 3 radioiodine therapies were performed with a cumulative dose of 700 mCi I-131. After termination of the therapy, the patient was initially without complaints, but approximately 6 months later, epiphora was noted, first only of the right eye and eventually of both eyes. A whole-body I-131 scan performed 1 year after final radioiodine therapy showed atypical tracer accumulation in both medial orbital regions. This finding was new compared with the scan that was done 1 year before. Dacryocystography revealed bilateral occlusion of the lacrimal drainage system. A review of the literature shows that epiphora and lacrimal duct alterations are rarely investigated and potentially underestimated side effects after high-dose radioiodine therapy.