The correlation between immunohistochemical detection (IH) of p53 protein and tumor response to preoperative chemotherapy and/or radiotherapy in advanced esophageal squamous cell carcinoma was evaluated. Fifty-six patients with advanced esophageal squamous cell carcinoma were included in the study. All patients were staged and diagnosed microscopically before treatment. Patients were divided into three groups: 17 patients treated with chemotherapy and radiotherapy preoperatively (group I) (cisplatin and 5-fluorouracil, cobalt-60 therapy; total dose 3000 Gy); 19 patients treated with chemotherapy only (group II); and 20 patients who did not receive preoperative therapy (group III). The response of the tumor tissue to preoperative treatment was evaluated macroscopically and microscopically in operated specimens according to the classification: CR, complete response; PR1, major partial response with regression of at least 50% of initial tumor mass; PR2, minor partial response with regression of less than 50% of initial tumor mass. In all 56 patients immunohistochemistry was used to detect anti-p53 antibody (Dako, DO-7) in normal mucosa and cancer tissue. The response of the tumor was similar in both group I and group II. p53 protein was not expressed in the normal esophageal mucosa. A high level of p53 in operated specimens was associated with unfavorable tumor response to preoperative treatment. Therefore, immunohistochemical detection of p53 protein can be considered to predict the outcome of preoperative therapy.