BACKGROUND The prognostic value of the Laurén classification and of c-erbB-2 oncogene overexpression has been described for gastric cancer. The aim of this study was to investigate the clinical significance of these factors in adenocarcinoma of the esophagus and/or gastroesophageal junction (GEJ). METHODS Forty-one adenocarcinomas of the esophagus and/or GEJ were reviewed for tumor stage, lymph node status, Laurén classification, and c-erbB-2 overexpression, as assessed by immunohistochemical analysis. RESULTS According to the Laurén classification, tumors were classified as intestinal-, mixed-, or diffuse-type (54%, 32%, and 15%, respectively). Diffuse-type tumors were associated with a significantly worse prognosis than were intestinal-type tumors (P = .018; log-rank test). The prognostic value of the Laurén classification was independent of stage (P = .048; Cox regression model). Overexpression of c-erbB-2 was detected in 24% of the tumors and was present exclusively in intestinal-type tumors and in intestinal-type areas of mixed-type tumors. Ten of the 30 stage III/IV tumors (33%) were c-erbB-2-positive, whereas none of the 11 stage I/II tumors (0%) overexpressed the oncogene product (P = .04; Fisher exact test). The prognostic value of c-erbB-2 overexpression was not independent of stage (P = .7; Cox regression model). CONCLUSIONS (1) The Laurén classification is an independent prognostic factor in adenocarcinoma of the esophagus and GEJ. (2) c-erbB-2 overexpression is limited to (areas of) intestinal-type tumors, indicating that intestinal- and diffuse-type tumors differ oncogenetically. (3) c-erbB-2 overexpression is associated with the stage of disease, indicating that it is a late event during tumor progression.