In the past decade we have witnessed an explosion in our knowledge of the molecular bases of hyperparathyroidism. In spite of the generally benign phenotype of parathyroid tumors, several of the well-recognized mechanisms in tumor biology are applicable to parathyroid tumorigenesis. The concept of evolution of nonneoplastic endocrine hyperplasia into a true tumor is as operative for the parathyroid tissue as for any other neoplasia. The molecular mechanisms underlying parathyroid tumor development, either on the ground of tissue hyperplasia or as neoplasia ‘ab initio’, are starting to be recognized. Oncogenes as well as tumor-suppressor genes and trophic factors appear to play a role in the process of parathyroid tissue growth. The unique opportunity of evaluating at least four distinct organs greatly contributed to the knowledge of the genetic basis of parathyroid tumor development, a field relatively undeveloped in comparison to that of other cancers.