PURPOSE: To assess the diagnostic accuracy of real-time ultrasound (US) for perithyroidal invasion of thyroid malignancy. MATERIALS AND METHODS: From January 2009 to December 2009, real-time US was performed on malignant thyroid nodules (largest diameter > or = 10 mm) located in the isthmus or attached to the adjacent tracheal wall, by a single radiologist who prospectively determined the presence or absence of perithyroidal invasion. RESULTS: Of the 60 malignant thyroid nodules examined, intraglandular location (n = 0), capsular attachment with clear perithyroidal fat (n = 15), perithyroidal fat infiltration without tracheal invasion (n = 43), and tracheal invasion (n = 2) were prospectively determined. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of real-time US diagnosis for perithyroidal invasion were 80%, 90%, 94.1%, 69.2% and 83.3%, respectively when the pathological result was used as reference standard. Real-time US accuracies for intraglandular location, capsular attachment with clear perithyroidal fat, perithyroidal fat infiltration without tracheal invasion, and tracheal invasion were 76.6%, 53.3%, 51.7%, and 85.0%, respectively. CONCLUSION: The results of the real-time US diagnoses indicate that this method may be useful for diagnosing perithyroidal invasion of thyroid malignancies. Hence, further research is needed to prove the use of diagnosing perithyroidal invasion of thyroid malignancies.