The purpose of a cervical screening program is to reduce morbidity and mortality from invasive cervical cancer. High-risk HPV DNA testing is more sensitive but less specific than conventional cytology. The increase in sensitivity results in doubling of positive subjects compared with Pap smear. However, lowgrade epithelial anomalies are over-represented when using HPV testing. Investigation and eventual treatment of many self-limiting conditions that would regress spontaneously result in needless psychological morbidity and increased costs. The same holds true for false positive results caused by a reduction in specificity. Moreover, the difference in sensitivity in favour of HPV testing has been demonstrated mainly at single testing. However, performance of repeated Pap smears at pre-determined time intervals greatly improves the accuracy of cytology. Limited adherence to prevention programs of women in lower socio-economic strata is among the risks related to the increase in cost of screening. The widespread utilization of different molecular tests not applied consistently according to the rules of good scientific practice has an economic, social, and psychological impact that seems to have greatly outweighed benefits. Indeed, a true reduction in mortality from invasive cervical cancer after the introduction of HPV testing has not yet been demonstrated. In addition, there is no general agreement on appropriate triage test for a positive HPV result, and guidelines are often not followed in general practice. Inappropriate testing increases costs without benefit, and potentially results in overtreatment. In European countries as well as in those countries where infrastructures are available, cytology is likely to remain the most cost-effective strategy in cervical cancer prevention, together with the implementation of HPV vaccination programs.