Introduction: False-negative thyroid fine-needle aspirates (FNA) are not well characterized. Methods: We correlated the results of all thyroid aspirations from 1997 to 2016 with histologic follow-up. Results: There were 13,733 aspirates, 2,112 (15.3%) resections, and 678 malignancies (32.1%). Eighteen (2.7%) false-negative cases were identified (interpretation, n = 6; sampling, n = 7; and new nodules, n = 5). Interpretive false-negative cases were significantly less likely when the indeterminate rate was greater than 13% (p = 0.01). Interpretive errors involved rare cells with poorly developed features of malignancy. Sampling errors were not associated with scant cellularity in the specimen. The majority of false-negative cases were not resected because of a clinical suspicion of malignancy. The sensitivity of FNA for 9-mm papillary carcinomas was 44.3%. Conclusion: In this cohort, the false-negative rate of thyroid FNA was 2.7% and the risk of malignancy for a benign diagnosis was 3.5%. Interpretative errors involved rare cells with poorly developed features of malignancy. There is little evidence that either the false-negative rate or the risk of malignancy of a benign thyroid FNA is different in patients who do and do not undergo resection.

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