The objective of this study was to find out whether C-160A single nucleotide polymorphism of the promoter region of the E-cadherin gene might be a potential genetic marker for identifying individuals at risk for gastric cancer (GC). To test this hypothesis, 412 GC patients and 408 controls were analyzed statistically. A PCR-restriction fragment length polymorphism assay was adopted for C-160A single nucleotide polymorphism detection. No statistical differences were found among CC, CA, and AA genotypes and the risk of GC, even stratifying according to age, sex, and area of residence. Similarly, genotype was not associated with intestinal or diffuse histotypes, or with cardia or noncardia carcinomas. In conclusion, the C-160A polymorphism is not associated with GC risk in the Italian population.