Squamous cell carcinoma evolving from squamous papilloma in both the upper and lower respiratory tract in the same patient is uncommon. The molecular mechanisms underlying the progression have not been well investigated. We herein describe a case of squamous cell carcinoma arising from respiratory papilloma in two independent occasions. The patient initially had oropharyngeal squamous cell carcinoma arising in a squamous papilloma at the age of 25 years. He subsequently developed squamous cell carcinoma in the left lower lobe of the lung, which was also associated with squamous papilloma, 8 years after the complete excision of the oropharyngeal lesion. Polymerase chain reaction-based broad-spectrum human papillomavirus DNA amplification and typing showed the presence of human papillomavirus type 11 DNA in both oropharyngeal and pulmonary tumors. Immunohistochemical studies showed that the expression status of p53, Rb, and p16 proteins was unaltered during tumor progression. These observations indicate that human papillomavirus 11-associated neoplastic transformation and tumor progression in the respiratory tract may not involve aberrant regulation of the p53 and Rb signaling pathways.