AIM: To evaluate the methylation status of CDH1, FHIT,MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma,30 intestinal-type gastric adenocarcinoma and 35 diffusetype gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher's exact test to assess associations between methylation status and clinicopathological characteristics.RESULTS: Hypermethylation frequencies of CDH1, FHIT,MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type.In diffuse-type, MTAP hypermethylation was associated with female gender.CONCLUSION: Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis,prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.