Twenty two patients are presented with histologic lesions on esophageal biopsy compatible with infection by human papillomavirus. Symptoms were uncharacteristic, there was no sex difference and the mean age was 40 years. Upper GI endoscopy showed the following: a) multiple ulcers in the middle esophagus, most of less than 10 mm in diameter, rounded or oval in shape, separated by normal appearing mucosa, well delimited erythematous margins, with a smooth white base; b) In five patients, multiple white elevated lesions were found in the middle esophagus, separated by normal appearing mucosa. One patient had 2 papillomas; c) In two cases there was an epidermoid carcinoma at 25 and 28 cm from the dental arcade. Biopsy taken at the border of the lesions were compatible with papilloma virus infection. The possible relation of the lesions with papillomavirus infection was established only on histologic criteria. The described lesions regress without treatment or with nonspecific treatment, some cases of our series have responded to empiric antiviral medication.