We generally choose transhiatal esophagectomy (THE) for patients with high risk for postoperative complications and for carcinoma of the lower thoracic esophagus, even if the tumor is in the advanced stage. In order to define indications for THE in esophageal cancer patients, we investigated 40 THE cancer patients according to the expressions of EGF/EGFR, p53 and p21. In patients with stage I, II, III and IV tumors, 5-year survival rates were 66.7%, 28.6%, 30.0% and 11.4%, respectively. The sites of first recurrence were the lymph nodes (n = 10) and single organs (n = 10). Dissemination (n = 3) and local recurrence (n = 2) were also seen as a first recurrence. According to EGF/EGFR, 5-year survival rate was 69% and 14% in the low and high EGF/EGFR groups, respectively. According to p53 expression, 5-year survival was 60% and 30% in the negative and positive groups, respectively; according to p21 expression, 5-year survival was 71% and 0% in the negative and positive groups, respectively. Significant difference was seen in EGF/EGFR and p21 groups. These data support less invasive surgery for some patients even for esophageal cancer patients. THE is a less invasive surgery, that also implies fewer curative procedure. Our results also showed that THE alone will be the only curative procedure necessary for some patients. We can determine therapeutic procedures using these new factors, and thus avoid unnecessary excess surgical stress in esophageal cancer patients.