Ultrasound (US) risk stratification systems (RSSs) have been developed to reduce the number of unnecessary fine-needle aspiration (FNA) biopsies in patients with thyroid nodules. Autonomously functioning thyroid nodules (AFTN) account for 5-10% of palpable lesions and are very rarely malignant. The present study was undertaken to investigate how RSSs classify AFTNs and whether RSSs are able to avoid unnecessary FNA biopsies in such cases.Patients with AFTN who had undergone US, scintigraphy and thyroid function evaluation from December 2016 to December 2017 were selected. US images were retrospectively reviewed and AFTN re-classified according to AACE/ACE/AME, ACR-TIRADS, ATA, BTA, EU-TIRADS, K-TIRADS and TIRADS. Risk class and indication for FNA were assessed.A number of 87 AFTNs from 85 consecutive patients were enrolled. A median diameter of 22 mm (range 10 to 59) was found, with an ovoid isoechoic nodule being the most frequent US presentation. When AFTNs were re-classified according to US RSSs, the most common categories were low- and intermediate-risk. AFTNs were assessed as being at high-risk/high-suspicion/malignant in 1 to 9%, with good agreement among AACE/ACE/AME, ATA, EU-TIRADS, K-TIRADS and TIRADS. Remarkably, FNA was indicated in 27 to 90% of AFTNs. A statistically significant difference among the systems was found; 8% of cases were non-classifiable by one or more US RSS.US RSSs prompt inappropriate FNA in a significant number of patients with AFTN.