Nuclear DNA content and nuclear DNA ploidy were measured in 36 Hürthle cell neoplasms (HCNs) to better define their potential roles in predicting the clinical behavior of these lesions. An EPICS V flow cytometer (Coulter Electronics, Hialeah, Fla) was used. Measurements were taken from paraffin-embedded tissue. Isolated nuclei were stained with propidium iodide. The study was conducted in a blinded fashion. Observed NDC and PDY patterns were classified as diploid, aneuploid, or suspicious. Twenty-nine lesions (81%) were diploid and seven (19%) were aneuploid. Twelve (33%) HCNs were malignant, 23 (64%) were benign, and one (3%) was indeterminate. Eight (67%) of 12 malignant HCNs were diploid and four (33%) of 12 were aneuploid. In comparison, 20 (87%) of 23 benign lesions were diploid and three (13%) of 23 were aneuploid. The indeterminate neoplasm was diploid. There were three deaths in this group of patients; all three had aneuploid neoplasms, and all had locally recurrent disease with distant metastases. There was a significant cross correlation between histologic features and DNA content with regard to outcome. These preliminary data suggest that NDC and PDY are not helpful in distinguishing histologically benign from malignant HCNs; however, they may be useful in determining prognosis.