Unexplained chest/epigastric pain is a common symptom in the general population. However, it has not previously been studied whether such pain could be a marker of subsequent gastrointestinal cancer. We aimed to estimate the risk of gastrointestinal cancers in a Danish 10-year follow-up study among patients with chest/epigastric pain, normal upper endoscopy, and no prior discharge diagnosis of ischemic heart disease (N = 386), compared with population controls (N = 3860). The overall 10-year risk of gastrointestinal cancer (stomach, colorectal, liver, and pancreas) was 2.9% for patients with unexplained chest/epigastric pain vs. 1.5% for controls. The adjusted relative risks or =1 year after upper endoscopy were 8.4 (95% confidence interval [CI], 2.6-27.5) and 1.2 (95% CI, 0.5-2.9), respectively. We found that patients with unexplained chest/epigastric pain have an increased risk of gastrointestinal cancer within the first year after upper endoscopy. Consequently, unexplained chest/epigastric pain might be an early gastrointestinal cancer symptom.