In 14 patients with occult persisting medullary thyroid carcinoma, tumor tissue was removed by microsurgical reoperation in 13 of 14 patients. This resulted in biochemical improvement in all but 1 patient and biochemical cure in 3 patients (21%). The lateral compartment of the neck or the upper mediastinum was involved in all but 1 patient. Before microsurgical reoperation, selective venous catheterization (SVC) for serum sampling along with serum calcitonin (CT) determination was done and compared to other localization methods. Tumor tissue could be localized correctly by SVC in 89% (CT gradient 1.21-2.02), computed tomography in 38%, and ultrasound in 28%. In patients with an elevated CT level after initial surgery and clinically occult disease, SVC is recommended for localization of tumor tissue. The affected side of the neck should be reoperated on with microdissection of the central and lateral compartment of the neck and the upper mediastinum. With this procedure, the cure rate of reoperation in patients with persistent occult MTC can be improved.