Abstract: Objective To analyze the short-term and long-term effects of thyroidectomy combined with isthmus resection in the treatment of micropapillary thyroid cancer, and to explore the most effective treatment for this disease. Methods Sixty patients with micropapillary thyroid cancer in our hospital from January 2007 to December 2008 were enrolled and assigned into control group (n=30) and observation group (n=30) according to the random number table. The control group was treated with total thyroidectomy combined with central lymph node dissection, and the observation group was treated with thyroidectomy combined with isthmus resection. The short-term effect (operation time, intraoperative bleeding volume, incision length, postoperative medication dosage, hospitalization time, parathyroid hormone and serum calcium level, hypocalcemia, hypothyroidism, recurrent laryngeal nerve injury and other complications) and long-term effect (total remission rate, recurrence rate, tumor-free survival rate and fatality rate of 5 years and 10 years) were compared between the two groups. Results The clinical related indexes of the observation group were better than those of the control group; the levels of parathyroid hormone and serum calcium in both groups were lower than those before the operation, but the decrease of the observation group was less than that of the control group; the incidence of postoperative complications in the observation group (10.0%) was lower than that in the control group (33.33%); there was significant difference between the two groups (all P<0.05). The total remission rate, recurrence rate, tumor-free survival rate and fatality rate of the observation group were similar to those of the control group in 5 and 10 years, with no significant difference (all P>0.05). Conclusion The short-term and long-term effect of thyroidectomy combined with isthmus resection is better than that of total thyroidectomy combined with central lymph node dissection in the treatment of micropapillary thyroid cancer. It can obviously improve the levels of parathyroid hormone and serum calcium, reduce complications, and reduce recurrence rate and fatality rate.