Thyroid fine-needle aspiration (FNA) is used to assess appropriate management of nodular thyroid lesions safely, but Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) and category IV (follicular neoplasm/suspicious for follicular neoplasm) lesions are problematic. This study aimed to evaluate the Afirma Gene Expression Classifier (GEC) results for lesions in those categories. Medical records of patients with thyroid FNA and GEC results were obtained from archived material. Results were compared to thyroidectomy histologic diagnoses. Among 66 patients with FNA results (47 women and 19 men aged 26-89 years [mean, 59.4 years]), surgical reports were available for 38. Afirma GEC results were "nondiagnostic" for 10 of 66 (15.2%), "benign" for 22 (33.3%), and "suspicious" for 34 (51.5%). Surgical diagnosis was available for 38 of 66 patients (57.6%); GEC results for 6 (15.8%) of these were "nondiagnostic," 27 (71.0%) were "suspicious," and 5 (13.2%) were "benign." One of 6 (16.7%) samples with "nondiagnostic" results, 1 of 5 (20%) with "benign" results, and 15 of 27 (55.6%) with "suspicious" results were malignant on histology. Papillary carcinoma was the most common tumor type (15 of 38; 39.5%). Afirma GEC results minimize the number of unnecessary operations. Afirma GEC testing may be reserved for FNAs with a category III diagnosis on follow-up cytologic examination. We recommend a conservative approach for "suspicious" Afirma GEC results if Hürthle cells are seen with FNA.