Background: Neoadjuvant chemoradiotherapy (NCRT) plus surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC); however, further analysis is needed to detail the histopathological characteristics of ESCC and their clinical significance after NCRT. This study aimed to present the pathological characteristics of ESCC and their association with prognosis after NCRT. Methods: All patients with ESCC who underwent NCRT followed by surgical resection at Sichuan Cancer Hospital (China) from January 2018 to December 2019 were included. Resection specimens of both the primary disease and lymph nodes were re-evaluated by an experienced pathologist. After NCRT, the pathological characteristics of the residual tumor were evaluated based on the Japanese residual tumor pattern, Mandard tumor regression grade (Mandard-TRG), local inflammatory infiltration classification, and lymph node status. Results: Among the 103 patients with ESCC included in this study, the pathological complete response (pCR) rate was 34% (35/103). The pCR rate of patients with poorly differentiated tumors (31/72) was higher (43.1%) than that of patients with well or moderately differentiated tumors (P<0.05). The residual tumor rate was 66% (68/103). A positive correlation was noted between the Japanese residual tumor pattern and Mandard-TRG (Kendall's tau-b =0.857, P<0.001). Tumor infiltration depth, lymph node positivity, moderate differentiation, and tumor recurrence were associated with poor oncological outcomes (P<0.05). Conclusions: Patients with poorly differentiated tumors can obtain an excellent short-term response; however, they have extremely poor long-term survival. For patients with moderately differentiated tumors, both the short- and long-term outcomes are poor. Lymph node status after NCRT is a prognostic factor for ESCC treated with NCRT.