The deleted in colorectal cancer (DCC) gene is a candidate tumor suppressor gene that may be associated with differentiation and proliferation of normal cells. Loss of heterozygosity (LOH) of 18q, where the gene is located, and absence of DCC protein expression have been associated with worse prognosis in certain subgroups of patients with colorectal adenocarcinoma. We studied the prognostic significance of loss-of-protein expression in 66 patients with resected gastric cancer with a high probability of relapse (T3, T4, N+). The DCC protein was detected with immunohistochemistry using an anti-DCC monoclonal antibody on paraffin-embedded sections. The DCC protein expression was present in 51 cases (77.3%) and absent in 15 cases (22.7%). Poorly differentiated and signet ring carcinomas had significantly lower expression than more differentiated tumors (p < 0.05) as did diffuse-type tumors compared to intestinal and mixed (p < 0.01). There was no correlation with proliferation rate, estimated immunohistochemically using an anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. Absence of DCC protein was an independent favorable prognostic factor (median survival 57 months vs. 18 months, p = 0.0176). The DCC protein expression was correlated with relapse site: all patients with distant metastases were positive for DCC staining, while one-third of patients with local/peritoneal relapse were negative (p < 0.01). In conclusion, DCC protein expression seems to be a significant prognostic factor in high-risk resected gastric cancer. Our results support previous data associating the DCC gene with differentiation and indicate that this gene may play a role in the metastatic potential of these tumors. These findings need to be confirmed by future larger studies.