Thyroid nodules are a common finding, especially in iodine-deficient regions. Ultrasonographic scoring systems such as the Thyroid Imaging Reporting and Data System (TIRADS) are helpful in differentiating between benign and malignant thyroid nodules by offering a risk stratification model. Depending on the constellation or number of suspicious ultrasound features, a fine-needle biopsy is recommended. However, none of the previous TIRADS publications considered the functional status of the nodules. Hyperfunctioning thyroid nodules (HTNs) were presumed to exclude malignancy with a very high negative predictive value. Particularly in regions where the iodine supply is low, most HTNs are seen in patients with normal thyroid-stimulating hormone levels. Therefore, thyroid scintigraphy is essential for the detection of HTNs. We investigated whether TIRADS identifies HTNs as nonsuspicious. Methods: We evaluated 615 HTNs (23.2 ± 10.0 mm in maximum diameter in 582 patients ([442 women, 57.7 ± 13.2 y old, and 140 men, 60.1 ± 12.7 y old) detected by 99mTc-pertechnetate or 123I scintigraphy. Before evaluating the scintigraphic appearance, all nodules were analyzed prospectively with sonography, using the TIRADS model referenced in Kwak et al., wherein fine-needle biopsy is recommended for TIRADS 4A or higher. We also investigated 2 subgroups, 42 nodules with available histology and 117 patients with subclinical or overt hyperthyroidism. Results: Whereas 15.9% of the nodules were classified as TIRADS 3 or lower and less than 0.1% as TIRADS 5, most of the nodules were classified as TIRADS 4A (29.3%), 4B (29.3%), or 4C (24.9%). Altogether, more than 80% of the autonomous thyroid nodules were classified as TIRADS 4A or higher, a grade that would result in a recommendation of fine-needle biopsy. Focusing on those 117 HTNs that were already associated with hyperthyroid laboratory values, the rates were similar: 81.2% were categorized as TIRADS 4A or higher (4A, 33.3%; 4B, 29.9%; 4C,17.1%; 5, 0.9%). In the subgroup of patients who underwent thyroid surgery, all nodules were benign, confirming the known negative predictive value of HTNs with regard to malignancy exclusion. Conclusion: Integration of thyroid scintigraphy into the TIRADS model is essential to prevent unnecessary fine-needle biopsy and thyroid surgery.