Partially cystic thyroid nodules (PCTNs) are common on ultrasound (US). However, there are insufficient data on the prevalence of thyroid carcinoma among such nodules. The purpose of this study was thus to evaluate the prevalence and differentiation of partially cystic thyroid cancers in US-guided fine needle aspiration (FNA).A total of 1342 consecutive patients with 1360 thyroid nodules underwent prospective US diagnosis and FNA biopsy. In total, 281 nodules (20.7%) were partially cystic lesions. The nodules were prospectively analyzed based on US features (ie, solid portion positions, shapes, margins, and microcalcifications) and US diagnosis (benign, suspicious, or malignant).Of the 281 partially cystic lesions, 22 nodules (8%) had inadequate FNA results, 14 nodules were diagnosed as malignant, 9 were suspicious for malignancy, and 236 were benign on FNA. Thirteen cancers were confirmed upon surgical histopathology examination or FNA, yielding a 4.6% rate of malignancy. Twelve of these cancers were papillary carcinomas, and 1 was an anaplastic carcinoma. The following individual sonographic characteristics had a statistically significant association with thyroid cancer: nodule composition (solid portion ≥50%, P = .000), eccentric solid portion (P = .001), irregular nodule shape (P = .000), microcalcification (P = .000), and intranodular vascularity (P = .001). The sensitivity, specificity, and accuracy of the US-based diagnoses were 84.6%, 84.0%, and 84.0%, respectively.Fewer than 5% of the partially cystic nodules in this FNA series were malignant. Sonographic characteristics can be used to prioritize nodules for FNA biopsy.