Human papillomavirus infection is important for both the development of papilloma and the progression of the papilloma-carcinoma sequence in the cervix, larynx, lung, and colon. Esophageal squamous cell papilloma is rare but important as a possible precancerous lesion. Esophageal papilloma has previously been thought to develop mainly as a result of chemical irritation by chronic gastroesophageal reflux. However, a few recent studies suggested a role for papillomavirus infection in esophageal tumorigenesis, although the exact route of transmission and invasion of the virus has not been fully elucidated. A case of esophageal squamous papilloma at the site of endoscopic injection sclerotherapy (EIS) for varices is reported. Papilloma development was followed up clinically during a 2-year period, and the papilloma was removed by endoscopic mucosal resection. Histological examination of the tissue confirmed the diagnosis of squamous cell papilloma. DNA analysis of the tumor showed integration of papillomavirus type 16 but not types 18 and 33. The surrounding normal mucosa did not contain any of the three virus types. Injury such as ulceration resulting from EIS may have provided a locus susceptible to the viral infection. The clinical course after EIS should be monitored carefully to detect papilloma formation.