BackgroundThyroid nodules are a very common finding in the general population. Fine-needle aspiration (FNA) has been recommended as the initial test for the evaluation of thyroid nodules. The trend on reporting as atypia of undetermined significance (AUS) has been significantly increased, but the malignant risk is still controversial among different studies. The aim of this study is to investigate the malignancy risk of thyroid nodules reported as Bethesda category III (AUS/FLUS) on initial FNA.MethodWe reviewed 272 papillary thyroid cancer (PTC) patients with suspicious thyroid nodules who underwent fine-needle aspiration and received surgical treatment during 2019 to 2020.ResultsOne hundred ten (40.4%) patients were diagnosed with PTC. Multivariate analysis showed that microcalcification (p = 0.037, OR = 2.260, 95% CI: 1.051–4.860), shape (p = 0.003, OR = 4.367, 95% CI: 1.629–11.705), diameters (p = 0.002, OR = 0.278, 95% CI: 0.123–0.631), anti-thyroglobulin antibodies (TGAb) (p = 0.002, OR = 0.150, 95% CI: 0.046–0.494), anti-thyroid peroxidase antibody (A-TPO) (p = 0.009, OR = 4.784, 95% CI: 1.486–15.401), and nodule goiter (p < 0.001, OR = 0.100, 95% CI: 0.046–0.217) were independent malignant risk factors in patients with thyroid nodule classified as Bethesda category III.ConclusionIn this study, malignant risk factors in patients with thyroid nodule classified as Bethesda category III were significantly associated with preoperative serum TGAb, A-TPO, microcalcification, irregular shape, and nodule diameters. Nodules with malignant factors should be carefully elevated; surgery may be the better option for those patients.