Multiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal dominant disease characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas. Sporadic forms of these tumors are more common than their inherited counterparts and share common genetic abnormalities. We have been studying the molecular genetics of sporadic pancreatic endocrine tumors to identify the tumor suppressor gene responsible for MEN1 by positional cloning. This review introduces the reader to the fundamentals of these molecular genetic techniques and outlines the general strategy used to isolate this gene.