Advances in molecular genetics have shed important new light on the understanding of the basis for human tumors. The application of these methods has allowed for characterization of endocrine neoplasms at a level of resolution that was not previously possible. A variety of molecular techniques have been applied to the study of parathyroid tumors at the DNA level. Studies of the clonal derivation of adenomas and hyperplasia suggest that these entities arise through fundamentally different mechanisms. The gene for parathyroid hormone (PTH) has been cloned and mapped within the human genome. In a small subset of parathyroid tumors, a rearrangement of the PTH gene has been described which may have contributed to their pathogenesis. A separate gene has been identified which appears to be responsible for the humoral hypercalcemia of malignancy. Chromosomal deletions which appear to be involved in the pathogenesis of multiple endocrine neoplasia type 1 have also been found in sporadic parathyroid adenomas. Characterization of tumors at the DNA level may make it possible to correlate specific genetic abnormalities with the biologic behavior of different parathyroid neoplasms and may be useful in distinguishing between adenoma, hyperplasia, and carcinoma.