ImportanceAlthough most thyroid nodules are benign, 10% to 15% of them harbor cancer. Thyroid ultrasonography is useful for risk stratification of nodules, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) classification provides recommendations for fine-needle aspiration cytology (FNAC) based on objective ultrasonographic features of these nodules.ObjectiveTo validate the concordance of ACR TI-RADS classification with Bethesda classification and histopathology.Design, Setting, and ParticipantsThis retrospective cohort study was performed to evaluate the concordance of ACR TI-RADS classification with Bethesda classification and histopathology and was conducted in Singapore General Hospital Outpatient Otolaryngology clinic in March 2021 to May 2021. Data analysis was performed in May 2021.Main Outcomes and MeasuresResults were deemed concordant when ACR TI-RADS recommendations aligned with Bethesda scores. Conversely, results were classified as nonconcordant with Bethesda scores and/or histopathology results when nodules that were recommended for FNAC yielded benign results or nodules that were not recommended for FNAC yielded malignant results.ResultsA total of 446 patients (370 women [83%]; mean [range] age, 60 [24-89] years) who underwent ultrasonography of the thyroid and ultrasonography-guided thyroid FNACs were identified. A total of 492 of 630 nodules (78.1%) were benign on FNAC (Bethesda II). Score 3 ACR TI-RADS nodules yielded the highest negative predictive values: 94.6% (95% CI, 92.9%-95.9%; P < .001) compared with Bethesda scoring and 100.0% (95% CI, 15.8%-100.0%; P = .003) compared with histopathology. Score 4 or 5 ACR TI-RADS nodules yielded positive predictive values of 2.8% and 16.2%, respectively, compared with Bethesda scoring and 6.1% and 66.7%, respectively, compared with histopathology. Small (<1.5 cm) ACR TI-RADS nodules of scores of 4 and 5 that were not recommended for FNAC yielded a malignant risk of 5.7% and 25.0% on Bethesda 5 and 6, respectively. On surgical excision, 5 of 46 (10.9%) ACR TI-RADS 4 nodules and 15 of 21 (71.4%) of ACR TI-RADS 5 nodules were confirmed to be malignant. Among nodules initially not recommended for FNAC, histopathology-proven cancer was found in 4 of 13 (30.7%) and 3 of 6 (50.0%) of nodules, respectively.Conclusions and RelevanceThese findings suggest that ACR TI-RADS score 3 nodules have a low risk of cancer and should be considered for FNAC only if nodules are 2.5 cm or larger. Patients with small (<1.5 cm) ACR TI-RADS 4 and 5 nodules should be appropriately counseled for FNAC to exclude cancer.