We have analyzed the expression of Gastrokine 1 (GKN1), one of the most abundant protein of gastric mucosa, in Helicobacter pylori-related preneoplastic and neoplastic gastric lesions. The GKN1 expression was down-regulated in 36 H. pylori-positive patients with respect to 29 H. pylori-negative subjects as evaluated by Western blot, reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, showing a progressive decrease from chronic gastritis to atrophy and intestinal metaplasia. Interestingly, in gastric cancer (GC) patients, GKN1 was undetectable in tissue tumoural areas but was instead expressed in the corresponding tissue non-tumoural areas. In conclusion our data suggests that GKN1 expression is related to the inflammatory damage of gastric mucosa and could be the related to the gastric cellular phenotype.