The predictors of malignancy are important for the decision of appropriate management in nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). Our aim was to determine the ultrasonographical, clinical, and biochemical predictors of malignancy in these patients. A total of 427 patients with cytologically Bethesda Category III (AUS/FLUS) thyroid nodules were included in this retrospective study. We divided the nodules into two subgroups according to the histopathology as benign and malignant, and compared the preoperative ultrasonographical, clinical, and biochemical findings. In overall, 427 patients with 449 AUS/FLUS nodules who had undergone surgery, the rate of malignancy was 23.4 % (105/449). When evaluated separately, the rate of malignancy was 25.8 % in nodules with AUS (82/318) and 17.6 % in nodules with FLUS (23/131) (p = 0.061). The vast majority of malignant specimens in histopathology consisted of papillary thyroid carcinoma (PTC) (n = 91, 86.7 %). Preoperative ultrasonographic features of 105 malignant nodules in histopathology were compared with the 344 benign nodules in histopathology. Anteroposterior/Transverse (AP/T) ratio was significantly higher in malignant group compared to benign group (p = 0.013). In multiple logistic analysis, we found that higher AP/T ratio and microcalcification were independently associated with malignancy (p < 0.05). The malignancy-associated cut-off value of AP/T ratio at maximum sensitivity and specificity was aeyen0.81. We did not find any correlation between malignancy and Hashimoto's thyroiditis in histopathology in multivariate analysis (p > 0.05). In Bethesda Category III nodules with higher AP/T ratio and microcalcification, surgery might be considered as a first therapeutic option instead of repeat fine-needle aspiration biopsy or observation.