c-fos was first identified as a viral oncoprotein, and has been studied in terms of its oncogenic function in tumorigenesis. Many experimental and clinical data indicated that c-fos expression plays a role in the progression of several types of carcinomas. However, some recent studies challenge this view as they indicate that c-fos has tumor suppressor activity. In the present study, we assessed c-fos protein expression in 625 consecutive gastric cancers immunohistochemically, and analyzed its relationship with clinicopathologic factors and survival. We found that a loss of c-fos expression is correlated with a more advanced stage, lymph node metastasis, lymphatic invasion and shorter survival, indicating that c-fos expression in gastric cancer cells is lost during progression and that this loss is associated with a poor prognosis. The above findings suggest that loss of c-fos expression has tumor suppressor activity in gastric cancer and we suspect that this suppressor activity might be related to the pro-apoptotic function of c-fos.