Human Papillomavirus (HPV) testing has been extensively studied in randomized controlled trials of primary cervical screening. Based on encouraging results concerning its high detection rates and a high negative predictive value for high-grade cervical intraepithelial neoplasia (CIN), HPV testing will probably replace cytology in future primary cervical screening. However, HPV testing is associated with more frequent false-positive tests compared to cytology. False-positive tests are defined as positive screening tests which are not subsequently confirmed with high-grade CIN. Several authors have claimed that the frequency of false-positive HPV tests could be reduced if an additional test was used to decide on referral for colposcopy of HPV-positive women. Data from the trials, however, do not support this claim. In fact, when compared to standard cytology screening and triage procedures, HPV testing leads to more screen-positive women being referred for colposcopy without having high-grade CIN, and to more women undergoing repeated testing. The only reasonable solution to the problem of false-positive tests appears to be a revised definition of a positive HPV screening test. However, further studies are needed to determine how this definition could be revised while at the same time keeping the high negative predictive value of HPV testing.