Aim: Geographic variation of upper gastrointestinal carcinomas (UGIC) was assessed in a high-risk region in northern China. Methods: Shexian, Linzhou, Yangcheng and Cixian are four counties with world age-standardized incidence rates (ASR) of esophageal cancer as high as 124.9, 99.5, 160.1, and 164.9 per 100,000 respectively for males, and 70.8, 68.8, 92.1, and 104.6 for females for 1998 to 2002. Geographically, Shexian is entirely mountainous, Linzhou and Yangcheng are mostly mountainous, and Cixian is one-third mountains, one-third hills, and the other third plains. The corresponding populations is 382,000, 982,000, 395,000 and 625,000 as in 2000. In the present analyses, the world ASRs of esophageal squamous cell carcinoma (ESCC), adenocarcinoma of the esophagogastric junction (AEG), gastric non-cardia carcinoma (GNCC), and the percentages of these in overall tumor ASRs for 1998 to 2002 were compared across the four counties to show geographic variation and clustering. Additionally, site-specific detection rates of precursors and cancers in our population-based endoscope surveys with local 40- to 69-year-old residents were also compared between a Cixian commune (2,013 surveyed) and a Shexian commune (1,514). Results: ASRs for ESCC, AEG, and GNCC combined amount to 210.5 to 325.8 per 100,000 in men and 117.5 to 185.7 in women, accounting for respectively 70.6 to 82.1% and 53.4 to 77.0 % of the all ASRs. In geographic distribution, the percentages of AEG and GNCC in UGICs increased from Cixian (males 32.8%, females 22.1%) to Yangcheng (50.7%, 38.6%) and Linzhou (52.7%, 41.4%), and further to Shexian (61.7%, 61.9); while that of ESCC decreased in the same direction from Cixian, to Yangcheng and Linzhou, and further to Shexian (67.2%, 77.9%; 49.3%, 61.4% and 47.3%, 58.6%; to 38.3%, 38.1%). Similarly, the detection rates of low-and high-grade intraepithelia neoplasia as well as cancers of the esophagus were significantly higher in the Cixian commune than the Shexian commune (8.7, 4.4, 0.7% vs 7.0, 3.2, 0.4% P=0.004); but the rates for the esophagogastric junction were systematically and significantly lower in the Cixian than in the Shexian commune (2.2, 0.5, 0.8 % Vs 3.3, 0.9, 1.7 %, P=0.001). Conclusions: Clustering of upper gastrointestinal carcinomas may suggest the existence of common risk factors, while geographic variation in topography/histology may be related to regional differences in carcinogen exposure. These observations identify a need for environment improvement, such as programs to improve drinking water conditions. To study high susceptibility in a historically low mobile population, international collaborative research in this region may prove to be very fruitful.