The proto-oncogenes epidermal growth factor receptor (EGFR) and erythroblastic leukemia viral oncogene homolog 2 (ERBB2), are involved in the development of diverse malignant tumors, including gastric cancer. We analyzed the association of SNPs EGFR-R521K and ERBB2-I655V with gastric cancer and premalignant gastric lesions in Mexican patients. Through restriction fragment length polymorphisms, we analyze both SNPs in the DNA from 155 patients with gastric cancer and premalignant gastric lesions, 121 controls, and 103 people from the Mexican general population. The frequencies of both SNPs did not differ significantly between any of the groups (chi2 p = NS); Odds ratio analysis showed that the alleles EGFR-521K and ERBB2-655V were not related to gastric cancer or premalignant gastric lesions in the Mexican population. Our data suggest that the EGFR-R521K and ERBB2-I655V polymorphisms are not suitable as markers for identifying individuals with a higher risk for developing gastric cancer in our population.