We describe 2 nonsmoking, nondrinking couples who developed human papillomavirus (HPV)-associated tonsillar cancer within 12 months of each other. After histopathologic evaluation, HPV L1, E2, E6, and LCR regions were amplified, and phylogenetic analysis of amplimers was determined. Quantitative polymerase chain reaction targeting HPV-16/18 L1 and E7 regions and P16 immunohistochemistry were performed. Tissues were HPV-16 positive, with distinct intercouple nucleotide differences and multiple unique intracouple similarities identified. Diffuse nuclear P16 expression was detected in tumor cells. This report demonstrates matching HPV-16 strains in 2 couples with concurrent development of tonsillar carcinoma who did not have other risk factors, revealing the potential infectious nature of oropharyngeal cancer.