Simultaneous multiple gastric cancers are rarely observed in clinical practice, and its association with p53 gene mutation has not been mentioned in any previous reports. We report a case of advanced gastric cancer with two primary lesions in the stomach who received total gastrectomy. Tumor and surrounding normal tissues from the surgical specimen were studied by using polymerase chain reaction-single strand conformation polymorphism analysis, restriction enzyme digestion method and direct sequencing. Point mutations of p53 gene at codon 248 (CGG-->TGG) were found in both primary tumor foci. The patient developed cancerous peritonitis eight months after the operation and expired six months later. This report suggests that p53 gene mutation can occur at an earlier stage in the tumorigenesis of gastric cancer than previously reported and it might be associated with an unusual clinical and pathological presentation.