BACKGROUND Multifocal chronic gastritis, associated to intestinal metaplasia, is considered a preneoplastic lesion, closely associated to intestinal type gastric cancer. OBJECTIVE To study the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) in areas of chronic gastritis and intestinal metaplasia in gastric biopsies of patients without cancer. METHODS Gastric biopsy samples from 34 patients without cancer (22 with multifocal atrophic gastritis and 12 with diffuse antral gastritis), were studied. Glands from areas of chronic gastritis and intestinal metaplasia and lymphocytes, were collected using laser microdissection of paraffin embedded samples. The analysis of 15 mono and dinucleotide microsatellites was used to assess LOH and MSI. RESULTS LOH and MSI were found in some of the markers in 55% (12/22) and 59% (13/22) of cases with intestinal metaplasia, respectively. Only one of 12 areas with diffuse atrophic gastritis had MSI and a different area had LOH (p < 0.05 or less, when compared with areas of multifocal atrophic gastritis). Three areas of normal epithelium in patients with multifocal atrophic gastritis, also had alterations. Most of these alterations were concordant with adjacent areas with intestinal metaplasia. CONCLUSIONS LOH and MSI was found in areas of intestinal metaplasia in more than half of the studied cases and in few areas of atrophic gastritis without intestinal metaplasia. These findings suggest that genotypic alterations may precede phenotypic modifications and that intestinal metaplasia is a preneoplastic lesion.