Cancer is a genetic disorder in which gene alterations are selected to provide growth advantage by oncogene activation and/or tumor suppressor gene inactivation. Even marked intra-tumor variation in the histologic pattern, which is common in gastric carcinoma, is considered a result of distinct oncogenic pathways coexisting together. The present review describes that most gastric carcinomas arise through two distinct genetic pathways: microsatellite instability targeting the mononucleotide tracts within coding regions of cancer-related genes and chromosomal deletion involving tumor suppressor genes. With regard to malignant phenotypes, microsatellite instability is associated with the intestinal histological type and chromosomal deletion is correlated with the growth pattern of gastric carcinoma. Moreover, the genetic instability would in turn lead to an increase in alterations of cancer-related genes. The corresponding cells gradually manifest diverse neoplastic properties, thus bringing about consecutive subclonal evolution of more malignant cells. We now have some dues leading to the characterization of phenotypic complexity of gastric carcinoma based on gene-inactivation mechanisms.