The purpose of this research was to develop a staging system for patients undergoing esophagectomy as part of neoadjuvant therapy that takes into account tumor regression grade and ypN-category (TRG-N). It is thought this would provide a more accurate prognosis than the American Joint Committee on Cancer AJCC postneoadjuvant treatment (ypTNM) stage groups. The predictive value of the conventional pathological T-category, which is based on the extent of invasion, may decrease after neoadjuvant treatment. Tumor response grade (TRG) is a measure of how well a patient’s cancer has responded to treatment; it can be used in conjunction with ypN-category to improve prognosis compared to AJCC post-neoadjuvant therapy (ypTNM) stage groups. About 210 patients with esophageal squamous cell carcinoma who had received neoadjuvant therapy prior to undergoing esophagectomy were evaluated as part of a training cohort. The validation group consisted of 107 patients from different medical facilities. The ypT-category and TRG were used to evaluate the surgically removed esophagi, with TRG being allocated using the Becker 4-level scale. Together with the ypN-category, these constituted the basis for the TRG-N classification scheme. The TRG-N system was compared to the current AJCC postneoadjuvant treatment (ypTNM) stage groups in terms of patient survival. Survival rates at 5 years for those diagnosed with ypTNM stage I, II, IIIA, IIIB, or IVA were 53.0%, 39.4%, 47.0%, 18.33%, and 0% in the training group. The percentages at each TRG-N stage I, II, III, and IV were as follows: 59.6%, 43.5%; 23.8%; 15.6%. The Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC) values for the TRG-N stage compared favorably to the ypTNM stage groups in terms of survival. The validation cohort yielded consistent findings. TRG-N stage (P=0.02), age (P=0.006), and sex (P=0.005) were all found to be independent predictive variables in a multivariate analysis. TRG-N stage provides more accurate prognostic information than AJCC post-neoadjuvant treatment (ypTNM) stage groups.