Squamous cell papilloma of the esophagus is a rare lesion involving less than 60 case reports worldwide. These lesions are generally asymptomatic but may at times grow and spread rapidly. One fatality, a result of massive dissemination, has been reported. Until recently, human papillomavirus had not been identified in association with esophageal papillomas. A second case, to the authors' knowledge, of esophageal papillomas associated with human papillomavirus is reported. The virus has been previously shown to be associated with abnormal squamous epithelium in and adjacent to esophageal carcinoma. The virus was identified from biopsy specimens obtained at endoscopy using DNA in situ hybridization techniques. The strain of human papillomavirus identified is similar to those found in the oropharynx and genital tract, raising the possibility of sexual transmission. This case also differs from the previous case report involving the human papillomavirus because of the patient's benign clinical course. Our case serves to highlight differences that are perhaps unique to the human papillomavirus. Multiple papillomas found in a proximal location within the esophagus seem to favor involvement of the human papillomavirus. Isolated lesions located distally appear more characteristic of chronic gastroesophageal reflux as an etiology. The syndrome of squamous cell papillomas involving the esophagus is reviewed in the article.