Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder 
characterized by the development of multiple hamartomatous polyps in the 
gastrointestinal tract. Polyps are most common in the colorectum (98% of 
patients) and the stomach (14%). Causative mutations for JPS have been 
identified in two genes to date, SMAD4 and BMPR1A. SMAD4 mutations are 
associated with a higher incidence of gastric polyposis. In this case report, we 
describe two patients with massive gastric polyposis associated with a SMAD4 
mutation. Both presented with anaemia and both had colonic polyps. Initial 
endoscopic findings revealed giant rugal folds suggestive of Ménétrier disease. 
However, as other possible gastropathies could not be differentiated on the 
basis of histology, a definitive diagnosis of JPS required additional mutation 
analysis. In patients with polyposis predominant in or limited to the stomach, 
establishing a diagnosis based solely on the pathological features of polyps can 
be challenging due to difficulties in differentiating JPS from other 
hypertrophic gastropathies. Mutation analysis should be considered early in the 
diagnostic process in cases of suspected juvenile polyposis, thus facilitating 
rapid diagnosis and adequate follow-up.