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Introduction: Surgery is the preferred treatment for recurrent differentiated thyroid carcinoma. However, scar tissue and tissue plane distortion can significantly limit the safety and the precision of the dissection. Careful preoperative planning is key to minimizing perioperative morbidity and positive margins. Case summary: We present a case of mixed thyroid carcinoma in a patient with multiple endocrine neoplasia type 1 syndrome. Following the initial surgery, the patient developed two recurrences, resistant to radioactive iodine treatment and had a history of positive margins. A year and a half later, the patient developed a third recurrence that was not palpable. We used a radioactive iodine-125 seed, preoperatively inserted under ultrasonography, to help retrieve the lesion intraoperatively and improve the precision of the dissection. Discussion: This is the first case report on the use of radioguidance with an iodine-125 seed to enhance the safety and exactitude of the surgical resection of a locally recurrent thyroid carcinoma. Although radioactive seed localization has been mostly used in breast cancer, this technique demonstrates great potential in becoming a useful adjunct to complex thyroid surgery in selected cases.