Esophageal infections may be caused by diverse pathogens that alter the mucosal lining and produce mild symptoms or sometimes critical clinical diseases with a high risk of mortality, particularly among the immunocompromised. The most common causes of infectious esophagitis are: herpes virus, candida, cytomegalovirus (CMV), and human immunodeficiency virus (HIV); human papilloma virus (HPV) infections are rare in Western countries. Endoscopic features of infectious esophagitis are specific for different agents; nonetheless, differential diagnosis is difficult and requires biopsy, cultures and brushing. We present the clinical case of a young woman admitted to the Department of General Surgery of A.O.U. Federico II, Naples, for a large, deep ulcerative lesion of the esophagus caused by HPV infection.