Surgical treatment and prognosis is different in esophageal, cardiac and distal gastric adenocarcinomas. Determination of the origin, in particular of adenocarcinomas situated at the gastroesophageal junction, may be difficult. It has been suggested that esophageal adenocarcinomas are characterized by a specific cytokeratin pattern, namely the CK7+/CK20- pattern. According to the same authors, this cytokeratin pattern is absent in gastric adenocarcinomas. The aim of our study is to evaluate if this cytokeratin pattern CK7+/CK20- is absent in cardiac and distal gastric adenocarcinomas. Therefore, we evaluated the combined immunohistochemical expression of CK7 and CK20 on paraffin-embedded material of 214 resection specimens for adenocarcinoma, comprising 66 esophageal, 73 cardiac and 75 distal gastric adenocarcinomas (UICC-classification). The adenocarcinomas were subtyped into intestinal- and diffuse-type according to the Lauren classification. The immunohistochemical staining was considered as positive if 50% or more of the tumor cells were stained. Statistical analysis has been performed applying the chi2-test. The tumors situated at the gastroesophageal junction, esophageal as well as cardiac adenocarcinomas, showed predominantly a CK7+/CK20- expression pattern (67 vs 68%), whereas this cytokeratin pattern is rather uncommon in distal gastric adenocarcinomas (31%, P<4 x 10(-5)). Independent of their localization, intestinal- as well as diffuse-type adenocarcinomas have a similar cytokeratin pattern. Our data show that the combined expression of CK7 and CK20 is different for the adenocarcinomas situated on both sides of the gastroesophageal junction compared to the distal gastric adenocarcinomas. However, in contrast to data in the literature, the combined expression of CK7 and CK20 has a low specificity in the distinction between esophageal and cardiac adenocarcinomas. This may suggest a similar origin (cell lineage) and thus may have an impact on therapeutic strategies.