OBJECTIVE: To retrospectively evaluate the risk of thyroid cancer in patients with hyperfunctioning thyroid nodules through ultrasonographic-pathologic analysis. MATERIALS AND METHODS: Institutional review board approval was obtained and informed consent was waived. From 2003 to 2007, 107 patients consecutively presented with hot spots on thyroid scans and low serum thyroid-stimulating hormone levels. Among them, 32 patients who had undergone thyroid ultrasonography were analyzed in this study. Thyroid nodules depicted on ultrasonography were classified based on size and categorized as benign, indeterminate, or suspicious malignant nodules according to ultrasonographic findings. The thyroid nodules were determined as either hyperfunctioning or coexisting nodules and were then correlated with pathologic results. RESULTS: In 32 patients, 42 hyperfunctioning nodules (mean number per patient, 1.31; range, 1-6) were observed on thyroid scans and 68 coexisting nodules (mean, 2.13; range, 0-7) were observed on ultrasonography. Twenty-five patients (78.1%) had at least one hyperfunctioning (n = 17, 53.1%) or coexisting (n = 16, 50.0%) nodule that showed a suspicious malignant feature larger than 5 mm (n = 8, 25.0%), or an indeterminate feature 1 cm or greater (n = 20, 62.5%) in diameter, which could have been indicated by using fine needle aspiration (FNA). Seven patients were proven to have 11 thyroid cancers in 3 hyperfunctioning and 8 coexisting nodules. All of these had at least one thyroid cancer, which could have been indicated by using FNA. The estimated minimal risk of thyroid cancer was 6.5% (7/107). CONCLUSION: Patients with hyperfunctioning nodules may not be safe from thyroid cancer because hyperfunctioning nodules can coexist with thyroid cancer nodules. To screen out these cancers, ultrasonography should be performed.