PURPOSE: Ultrasound-guided fine needle aspiration (US-FNA) in thyroid nodules is presently most commonly used to identify whether these nodules are benign or malignant. However, atypical or follicular lesions of undetermined significance (AUS/FLUS), as categorized in the Bethesda System for reporting the results of FNA, cannot be classified as benign or malignant. Therefore, several clinical factors should be considered to assess the risk of malignancy in patients with AUS/FLUS. The purpose of the present study was to determine which clinical factor increased the risk of malignancy in patients with AUS/FLUS. METHODS: A retrospective study was done on 129 patients with fine needle aspiration categorized as AUS/FLUS from January 2011 through April 2015. Univariate and multivariate analyses were performed to assess the independent effect of risk factors such as age, sex, size of nodule, atypical descriptors, and ultrasonography criteria for malignancy. RESULTS: We identified that the presence of spiculated margin (odds ratio [OR], 5.655; 95% confidence interval [CI], 2.114-15.131; P = 0.001), nuclear grooving (OR, 3.697; 95% CI, 1.409-9.701; P = 0.008), irregular nuclei (OR, 3.903; 95% CI, 1.442-10.560; P = 0.001) were shown to be significantly related to malignancy on univariate and multivariate analyses. CONCLUSION: We recommend that surgical resection of thyroid nodules be considered in patients with AUS/FLUS showing the histologic findings such as nuclear grooving, irregular nuclei along with spiculated margin of ultrasonographic finding.