BACKGROUND Despite recent advances in surgical and multidisciplinary treatment, the prognosis for patients with adenocarcinoma of Barrett's esophagus remains poor. The low prognostic accuracy of even surgical pathologic TNM staging suggests that additional parameters are necessary in determining the prognosis. METHODS In a retrospective analysis of 50 patients who underwent transhiatal or transthoracic esophageal resection due to adenocarcinoma of Barrett's esophagus, a quantitative DNA analysis using image cytometry was performed in addition to the TNM classification and usual morphological criteria. At the time of DNA analysis the histomorphological parameters and survival time were not known. RESULTS The main prognostic parameter was the curativity (R classification) of the operation. Considering only patients after R0 resection, a multivariate analysis identified the DNA ploidy, the depth of tumor infiltration and distant metastases of prognostically independent factors. Furthermore, within pT2 and pT3 tumors, which account for 80% of all the tumors, DNA ploidy allows an additional prognostic differentiation which is not possible with pT stage alone. CONCLUSIONS Patients with a diploid or tetraploid tumor without distant metastasis and a tumor stage pT1-pT3 should have curative (R0) resection. In case of an aneuploid DNA content or a pT4 tumor resection alone shows no advantage as compared to palliative nonoperative procedures.