It is clear that the DNA content of endocrine cells is influenced by factors other than neoplastic change and transformation. Although it can be concluded that, in general, the DNA content of neoplasms is increased, it is less clear whether this increase in DNA content is the cause or the effect of neoplastic transformation. The actual consequences of an increased DNA content are still largely unknown. However, based on a substantial body of data on the measure of nuclear DNA content in thyroid neoplasms, several conclusions appear to be reasonable. First, the measurement of nuclear DNA content and ploidy analysis are not sufficiently reliable parameters upon which to distinguish a benign from a malignant thyroid neoplasm. Therefore, this parameter has failed to live up to the expectation that it would be a powerful diagnostic tool. Second, the measurement of nuclear DNA content is useful after a histomorphologic diagnosis has been made since it correlates very well with the prognosis and clinical outcome of the patient. It is clear that aneuploid thyroid carcinomas are responsible for earlier recurrence, an increased likelihood of distant and diffuse metastases, and an increased incidence of death compared with diploid thyroid carcinomas. Except for the rare occasion, diploidy implies a uniformly long-term survival whereas aneuploidy is associated with a variable clinical course. Irrespective of histomorphology, lethal lesions of the thyroid are invariably aneuploid, whereas lesions associated with prolonged survival or a favorable outcome can be either diploid or aneuploid. Aneuploidy in well-differentiated thyroid carcinoma is more likely in older patients, in less well-differentiated neoplasms, and in neoplasms infiltrating beyond the thyroid capsule. Age, type of neoplasm, extrathyroidal extension, and recurrent disease all appear to be more important prognostic variables than is nuclear DNA content. However, nuclear DNA content can increase the prognostic power of these variables and consequently may come to be increasingly useful in the management of some patients with thyroid neoplasms. After a histomorphologic diagnosis has been made, the measurement of nuclear DNA content and a determination of the DNA ploidy may have significant prognostic value.