Human papilloma viruses (HPVs) are known to infect the genitourinary tract, the skin, the anal canal, and the upper respiratory tract. Esophageal papillomas and especially HPV-induced squamous papillomas of the esophagus are rare. The authors report a case of extensive HPV-induced esophageal polyposis, which was probably sexually transmitted. The 53-year-old female patient presented with chronic diarrhea and had occult blood in the stool. She underwent esophagogastroduodenoscopy, at which time multiple esophageal polyps were observed and biopsy specimens obtained. Histologic evaluation was consistent with benign papillomas. Polymerase chain reaction and DNA hybridization of the biopsied tissue specimens confirmed the diagnosis of HPV infection. Because of our observation and because of HPV's relationship to cervical and esophageal cancer, further evaluation of HPV as the cause of esophageal papillomatosis and as a risk factor for esophageal cancer is warranted.