Compared to hereditary medullary thyroid carcinoma (MTC), sporadic MTC tends to be unicentric and confined to one lobe. Patients with sporadic MTC usually undergo total thyroidectomy because of a possible hereditary or bilateral process. We evaluated the usefulness of germline RET oncogene mutation analysis in surgery for apparently sporadic MTC and performed unilateral surgery on patients without detectable mutation. In 36 patients with a preoperative diagnosis of apparently sporadic MTC, we performed germline RET oncogene mutation analyses: before surgery in 8 recent patients and after surgery in 28 who had been treated before 1996. Of the latter, 5 had bilateral MTC. DNA samples were extracted from their peripheral blood, and the polymerase chain reaction products of the RET proto-oncogene were analyzed using single-strand conformation polymorphism analysis and the direct sequencing methods. Before 1996 we often performed total thyroidectomy but changed to hemithyroidectomy thereafter, except in one patient with associated Graves' ophthalmopathy. Our minimal standard practice included systematic central and ipsilateral neck dissection. The outcome was assessed in terms of gastrin- and calcium-stimulated plasma calcitonin levels. Germline RET mutations were found in six patients. Five of these patients had bilateral MTC, whereas all 30 patients without mutation had unilateral disease. Hemithyroidectomy in seven of our recent patients resulted in normalization of plasma calcitonin levels in all, although four were found to have microscopic lymph node involvement. In conclusion, hemithyroidectomy with systematic central and ipsilateral neck dissection is an appropriate procedure for patients with sporadic MTC without detectable germline RET mutations.