The purpose of this article is to review the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. Current data demonstrate that approximately half of all tonsillar cancer is HPV positive. Moreover, patients with HPV positive cancer have a less risk of relapse and have a longer survival compared to patients with HPV negative tonsillar cancer. The longer survival is not dependent on that HPV positive tonsillar cancer is more sensitive to radiation therapy. However, in general HPV positive cancer exhibits less genetic instability in that it has a lesser degree of aneuploidy and fewer chromosomal aberrations when compared to HPV negative tonsillar cancer.