PURPOSE: Allelic loss on chromosome 18q is a hallmark of presence of a tummor represser gene. Recently, DPC4 (deleted in pancreatic carcinoma, locus 4), a candidate tumor suppressor gene, has been localized at 18q21. Inactivation of DPC4 gene was reported in pancreatic carcinomas, coloretal carcinomas, and prostatic carcinomas. The aim of the present study was to determine if it might be altered in stomach cancer. MATERIALS AND METHODS: We tested for DPC4 gene mutations and allelic status at 18q21 using a modified 'cold SSCP' method in 48 primary gastric carcinoma and correlated the findings with various clinicopathologic characteristics of the patients. RESULTS: The frequency of mutations in primary gastric cancer was 27.1% (13/48). Mutations of exon 1, 8, 10 were found in 2 (4.1%), 4 (8.2%) and 7 cases (14.6%), respectively. DNA sequencing of 13 cases with DPC4 mutations identified six cases (46.1%) with substitution, four cases with deletion (30.7%), and two cases (23.1%) with insertion. No significant difference was observed in the frequency of DPC4 mutations in terms of other various clinicopathologic characteristics. CONCLUSION: These findings suggest that DPC4 mutations may play a significant role in the establishment and progression of the primary gastric cancer.