BACKGROUND:: Familial occurrence of Ménétrier disease is very rare and has been reported only in few instances. METHODS:: affected patients from a large pedigree were evaluated at the clinical, endoscopic, and pathological levels. RESULTS:: affected members presented with gastropathy of variable severity but without protein loss. Endoscopy and pathology findings were consistent with Ménétrier disease. However, gastric TGF-α immunohistochemistry and real time PCR showed no increase in TGF-α expression. CONCLUSIONS:: We describe a unique, four-generation pedigree with autosomal dominant gastropathy exhibiting the typical clinical, endoscopic, and pathological findings of Ménétrier-like disease, though in the absence of protein loss and with normal levels of gastric TGF-α. Members of this family may be affected by a novel and previously unrecognized hereditary form of gastric hyperplasia.