Intraoperative pathologic diagnosis of thyroid neoplasms. Report on experience with 504 specimens. Intraoperative pathologic examination with frozen section (FS) was performed on 504 specimens of thyroid tissue obtained from 457 patients over a period of 9 years. After examination of permanent sections (PS) a malignant neoplasm was diagnosed in 57 specimens (11.3%); 50 (87%) of these were primary thyroid carcinoma, four (8%) metastatic carcinoma, and three (5%) malignant lymphoma. The FS diagnosis was "benign" in 448 (88.9%), "malignant" in (30) 5.9%, and "deferred" in 26 (5.2%). The sensitivity of FS diagnosis of malignancy was 53% and the specificity and positive predictive value 100%. The negative predictive value was 97.8% and overall accuracy 97.9%. The PS disclosed a malignant neoplasm in 62% of specimens in which FS diagnosis was "deferred." Sixty-eight percent of papillary carcinomas, 87% of undifferentiated carcinomas, and a single case of medullary carcinoma were diagnosed with FS examination. A FS diagnosis of malignancy was not made in any of the ten specimens containing follicular carcinoma; in all ten the neoplasms were well-differentiated and eight were encapsulated and minimally invasive. The inability to diagnose follicular carcinoma intraoperatively with FS is the most significant factor accounting for the relatively low sensitivity of FS diagnosis of malignant thyroid neoplasms. 