Human papillomavirus (HPV) was recently identified as a risk factor for oropharyngeal squamous cell carcinoma (SCC) independent of tobacco and alcohol use. The prognosis of patients with HPV-related oropharyngeal carcinomas is better than that for patients with non-HPV-related cancers. Researchers and clinicians can test for HPV infection in cancer by (1) testing directly for HPV DNA and (2) testing for overexpression of the downstream p16 protein; there is currently no consensus regarding which is the better test. The chances of developing a reliable oropharyngeal HPV screening test for high-risk populations are promising. Such a test would allow for secondary prevention by identifying individuals with precursor or early-stage cancerous lesions that are more amenable to treatment. HPV testing has particular significance in SCC of an unknown primary site in head and neck cancer. Successful HPV testing of nodal metastasis can localize cancer specifically to the oropharynx. The optimal evaluation for SCC of an unknown primary in the head and neck has yet to be determined. Some studies have shown that the tonsillar fossa is the most probable primary site, followed closely by the base of the tongue. Biopsies often miss tonsillar carcinoma in the deep crypts of the lymph tissue, as well as in those rare cases in which the primary tumor is located contralateral to the metastatic lymph node. Recently, there has been an increase in the number of reports of diagnosed synchronous bilateral HPV-related tonsillar carcinomas. This increase has profound implications for the surgical approach of SCC of an unknown primary site in the head and neck and in tonsillar carcinoma, and it supports the need for bilateral tonsillectomy. We present 2 cases of incidentally discovered synchronous bilateral tonsillar carcinoma, and we review the literature.