Non-neoplastic proliferative lesions of endocrine cells have been described throughout the gastrointestinal tract and pancreas. A multistep continuum from hyperplasia and dysplasia to neoplasia originally was identified and systematically defined for histamine-producing enterochromaffin-like (ECL) cells of the gastric corpus. More recently, a similar classification system was devised for gastrin (G)- and somatostatin (D)-producing cells in the duodenum. Preneoplastic lesions of the endocrine pancreas still lack a solid and widely accepted definition of a multistep growth process. Similarly, in spite of reports of carcinoid-associated endocrine cell hyperplasia, there is no systematic definition of nonneoplastic lesions of the endocrine cells of the ileum, appendix and colorectum.