We describe 2 patients who had human immunodeficiency virus (HIV) infection and who first developed human papillomavirus (HPV)-related anal squamous cell carcinoma and later, oral squamous cell carcinoma. At the time each patient developed oral cancer, they were responding well to antiretroviral therapy with undetectable viral loads. Careful screening for oral cancers may be indicated in HIV-infected patients with HPV-associated anal cancer.