We evaluated histomorphological findings in 92 surgical resection specimens of locally advanced esophageal adenocarcinomas after neoadjuvant cisplatin-based chemotherapy. Tumor response to neoadjuvant chemotherapy was determined using a system encompassing three tumor regression grades based on the estimation of the percentage of residual tumor tissue of the primary tumor site in relation to the macroscopically identifiable previous tumor bed. The significance of this system was validated by correlation of the tumor regression grades with the corresponding clinicopathological characteristics and patient survival. Seven patients (7%) had complete tumor regression (grade tumor regression grade 1), 48 patients (52%) had subtotal or partial tumor regression (tumor regression grade 2: 1-50% residual tumor), and 37 patients (40%) had minimal or no regression (tumor regression grade 3: >50% residual tumor). Tumor regression was significantly associated with posttreatment complete tumor resection status (UICC R0 status; P=0.016), tumor category (UICC pT category; P<0.001), and with the absence of either lymph node metastases (P=0.001) or lymphatic invasion (P<0.001). Survival analysis showed a significant prognostic relevance of the applied regression system in univariate (P<0.001) and multivariate analyses as a single independent factor (P=0.024). We conclude that the effect of preoperative chemotherapy in esophageal adenocarcinomas can be assessed by the determination of histological tumor regression, providing highly valuable prognostic information, which may even exceed the prognostic impact of the current TNM classification of these tumors. Therefore, we strongly recommend the implementation of a standardized tumor regression grading system in pathological reports of esophageal adenocarcinomas treated by neoadjuvant chemotherapy.