The postoperative outcome (including clinicopathologic features) in 19 patients with differentiated thyroid cancer of the isthmus was investigated to develop more appropriate surgical strategies for these lesions. The extent of thyroidectomy, including neck dissection, tumor size, nodal involvement, and other clinical features were evaluated. The incidence of intraglandular dissemination was about 16% in all patients. Analysis of regional node metastatic distribution revealed no definite metastatic pattern. In addition, there was no apparent correlation between tumor size and nodal involvement. Two of the six patients who underwent total thyroidectomy suffered permanent postoperative hypoparathyroidism. It is thus recommended that isthmusectomy, including an adequate edge of surrounding normal thyroid tissues of each lobe and modified or limited neck dissection when cervical nodes are palpably enlarged is sufficient as an appropriate primary surgical procedure for differentiated carcinoma of the thyroid isthmus.