Background and Aims: The metabolic profile andmorphologic aspects of normal and pathologic humangastric mucosa were studied. The aim of the presentresearchwas the application of ex vivo high-resolutionmagic angle spinning magnetic resonance spectroscopy(HR-MAS MRS) to the human gastric tissue to getinformation on the molecular steps involved in gastriccarcinogenesis and the identification of biochemicalmarkers useful for the development of in vivo MRSmethodologies to diagnose gastric pathologies inclinical situations.Methods: Twelve normal subjects, five withautoimmuneatrophic gastritis, five with Helicobacter pyloriinfection, and five with adenocarcinoma were examined.Ten biopsies were taken during endoscopy fromeachpatient. Specimens from carcinoma were alsoobtained during gastrectomy. Of the 10 biopsies, 4 wereused for histologic evaluation, 4 were fixed in glutaraldehydeand processed for transmission and scanningelectron microscopy, and 2 were immersed in liquidnitrogen and stored at 85C for monodimensional andbidimensional ex vivo HR-MAS MRS analysis.Results: Ex vivo HR-MAS MRS identified glycine,alanine, free choline, and triglycerides as possiblemolecular markers related to the human gastric mucosadifferentiation toward preneoplastic and neoplasticconditions. Ultrastructural studies of autoimmuneatrophic gastritis and gastric adenocarcinoma revealedlipid accumulations intracellularly and extracellularlyassociated witha severe prenecrotic hypoxia and mitochondriadegeneration.Conclusions: This is the first report of synergicapplications of ex vivo HR-MAS MRS and electronmicroscopy in studying the human gastric mucosadifferentiation. This research provides useful informationabout some molecular steps involved in gastriccarcinogenesis. The biochemical data obtained ongastric pathologic tissue could represent the basis forclinical applications of in vivo MRS