Verrucous squamous cell carcinoma (VSCC) is a rare esophageal tumor histologically defined as a well-differentiated subtype. We present a rare case that was diagnosed as esophageal VSCC preoperatively. A 62-year-old Japanese male was referred to our hospital for further evaluation, presenting with anorexia and postcibal vomiting. An esophagogastroduodenoscopy (EGD) examination showed esophageal stricture with white-colored papillary nodules in the lower esophagus. We performed repeated superficial endoscopic biopsies of the lesion, but the histological findings showed nonspecific changes. With an endoscopic boring biopsy, the lesion showed an endophytic growth pattern, well-differentiated SCC with minimal cellular atypia and rare mitosis, and mature squamous epithelium with extensive keratinization. We preoperatively diagnosed the lesion as esophageal VSCC, and we performed a video-assisted thoracoscopic subtotal esophagectomy and cardiectomy with the patient in the prone position. Histological findings revealed that the invasive well-differentiated SCC extended into the esophageal adventitia and the stomach wall with a pushing border. Regional lymph node metastasis and vascular invasion were negative. The expression of Ki-67 was distributed mainly in the basal cells rather than parabasal cells. Without a conclusive diagnosis, a certain degree of diagnostic prediction is possible by understanding the clinical manifestations, macroscopic form and histology around the basal cells. It is helpful to obtain the high accuracy provided by an endoscopic biopsy including the basal layer in order to avoid the diagnostic dilemma that is often presented by esophageal VSCC.