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Background & Objective: Gastric cancer is the 2nd cause of cancer mortality after lung cancer. Approximately 12% of all cancer death are due to gastric cancer. Tumorgenesis is thought to be a multistep process involving a series of genetic changes in oncogenes and suppressor genes. The most common cancer-related genetic change known in human tumors is P53 mutation, particularly in gastric cancer. This study was done to determine P53 gene mutations in gastric cancer. Materials & Methods: This study was performed on 44 biopsy from patients with gastric cancer during 2002 in 3 hospitals in Tehran. For determination of P53 gene mutations was performed PCR-SSCP methods. Results: The patients group comprised 31 males and 13 females (Average age, 60.8 years Ranging from 34 to 84 years). 36 cases (81.8%) intestinal type, 5 cases (11.4%) were diffuse type and 3 cases no defined. 44 gastric cancers of gastric tissues were screened for the mutations of P53 gene mutations in exons 5-8 using the PCR-SSCP analysis. After polyacrylamide gel electrophoresis, 9 patients (20.5%) showed an apparent electrophoretic mobility shift between the cancer and other normal samples. One mutation in exon 5 (11.1%), 2 were detected in exon 6 (22.2%), 3 were found in exon 7 (33.3%) and 3 were detected in exon 8 (33.3%). The mutation rate was 7 of 36 (21.2%) in intestinal type and 2 of (40%) in diffuse type. No significant correlation between P53 gene mutations and age and genus was found. Conclusion: This investigation showed the rate P53 gene mutation (20.5%) in gastric cancer in our society.