Cidofovir, a purine nucleotide analogue of cytosine, is a promising new drug that acts against a wide number of DNA viruses. In 1997, the Food and Drug Administration approved intravenous cidofovir for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Recent studies have shown cidofovir (1% gel or cream) to be effective for the treatment of recalcitrant and unmanageable viral cutaneous lesions induced by herpes, pox, and papillomavirus families. We report the case of a 45-year-old man who had been diagnosed as having acquired immunodeficiency syndrome in 1995. Recalcitrant to conventional therapies, the human papillomavirus lesions on his gingival mucosa were successfully treated with cidofovir 1% cream. To the best of our knowledge, this is the first case in which topical cidofovir has been used for the treatment of a human papillomavirus infection of the oral mucosa.