We aimed to investigate the diagnostic accuracy of ultrasound (US)-guided fine-needle aspirates (FNAs) obtained from 854 consecutive Danish patients with a scintigraphically cold thyroid nodule in a borderline iodine-deficient area. Clinical, sonographic, and pathological findings in patients with a cold thyroid nodule undergoing US-guided FNA were prospectively registered. 408 patients underwent thyroid surgery, resulting in 50 cancers and in addition 37 patients had an incidental finding of papillary thyroid microcarcinomas. Based on the diagnostic FNA, we found sensitivity and specificity for malignancy of 73.9 and 99.2%, respectively. The positive and negative predictive values of a diagnostic FNA for malignancy were 89.5 and 97.7%. We identified 6 false-negative and 2 false-positive diagnoses. Solid versus cystic feature of the nodule, as well as >2 high-risk US features, were predictive for malignancy. Cancer incidence was 13% among females and 9% among males. The accuracy of a diagnostic set-up based on clinical examination, scintigraphy, US, and US-guided FNA was determined with a 48% rate of histopathological validation in the cohort. The overall thyroid cancer incidence has increased worldwide, but our results suggest that the most frequent occurring cancer is an incidental papillary thyroid microcarcinoma of which the clinical significance has yet to be established.