The objective of the current study was to determine the risk of malignancy in patients with thyroid nodules with cytology of indeterminate follicular and indeterminate Hurthle cell neoplasm (HN). The cytologic diagnosis of follicular neoplasm (FN) or HN remains a diagnostic challenge. Often, surgery is recommended for such lesions. A retrospective analysis was performed on 80 patients who underwent thyroid surgery following a diagnosis of indeterminate FN and indeterminate HN in thyroid fine-needle aspiration biopsy. Sex; age; family history of thyroid cancer and radiation exposure; coexisting thyroid conditions, such as solitary nodule; multinodularity; cytologic diagnosis; sonographic features; type of surgical treatment; and histopathologic results were recorded. Of the 80 patients, 52 (65%) had FN on fine-needle aspiration biopsy cytology and 28 (35%) had HN. A total of 23 patients (28.7%) had primary thyroid cancers on surgical pathology, and 57 (71.3%) had benign diagnoses. Univariate analysis showed no differences between the benign and malignant groups by sex, nodule size, family history of thyroid cancer, history of radiation exposure, presence of solitary nodule or multinodularity in the nodular features. In multivariate binary logistic regression analysis, the factors that were statistically significant predictors of malignancy were microcalcification [odds ratio (OR), 10.9; 95% confidence interval (CI), 2.18-54.7; P = 0.004], being older than 45 years (OR, 4.2; 95% CI, 1.25-14.63; P = 0.02]. The independent predictors of malignancy in FN and HN are micorcalcification and being older than 45 years, the use of which may predict the risk of thyroid cancer.