BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) provides uniform diagnostic terminology for communication between pathologists and clinicians. Each diagnostic category is associated with a specific risk of malignancy and a recommendation for its management. The indeterminate diagnostic categories of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) present a major challenge for both pathologists and clinicians. We report our institution's 3 years' experience with the AUS/FLUS category and follow-up of these patients. METHODS: A retrospective analysis was conducted for all thyroid fine-needle aspirations (FNAs) between July 2010 and July 2013. During this period, 9242 nodules from 4916 patients were reported according to the BSRTC guidelines. We adopted the AUS terminology in our practice to refer to both AUS, and FLUS. RESULTS: Of the 4916 patients, 347 (7%) were diagnosed as AUS. The malignancy risk for patients who underwent surgical resection after initial diagnosis of AUS was 22.8%, whereas that for patients who underwent a second FNA and surgical resection was 36%. When we included patients with second FNA and without surgery, the malignancy risk was 15.7%. CONCLUSIONS: The malignancy risk for AUS reported in the present study is consistent with those reported previously and is higher than those anticipated according to the Bethesda System. This supports that a multimodal approach (clinical, radiologic, and cytopathologic) is necessary for the management of thyroid nodules diagnosed as AUS. Therefore, we suggest that the recommendation for repeat FNA following an initial diagnosis of AUS should be based on a multimodal approach for each particular patient. Cancer (Cancer Cytopathol) 2014; 122: 604-10. (C) 2014 American Cancer Society.