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Current randomized clinical trials have shown that the quadrivalent human papillomavirus (HPV) vaccine can reduce the morbidity of precancerous lesions associated with HPV infection of vaccine-related subtypes. However, to date, there is no definite evidence showing the vaccine reduces the incidence of invasive cervical carcinoma.We present two cases––one young, vaccinated woman who developed cervical carcinoma that was unrelated to HPV and another who developed cervical carcinoma secondary to infection with an HPV subtype not covered by the vaccine. Both patients were treated successfully and remained well without evidence of cancer.Long-term follow-up data are needed to evaluate the prophylactic effectiveness of the current HPV vaccine. These cases could represent non–vaccine-related HPV infections. Young women must be thoroughly counseled about the efficacy and limitations of the vaccine and about continuing lifelong screening even after vaccination.