Several studies have examined the role of tests for human papillomavirus (HPV) in screening for cervical cancer but as yet the relevance is unclear. We looked at HPV testing for types 16, 18, 31, and 33 on material taken at the time of a cervical smear in 2009 eligible women having routine screening. Women with any degree of dyskaryosis or high levels of one of these HPV types were referred for colposcopy. 44% of the cervical intraepithelial neoplasia (CIN) lesions of grade 2/3 detected had negative cytology and were found only by HPV testing. A further 22% of the CIN 2/3 lesions were positive for HPV but showed only borderline or mild cytological changes. The positive predictive value of HPV testing was 42%, which was similar to that for moderate dyskaryosis. HPV types 16 and 31 were more sensitive and specific for CIN 2/3 than were types 18 or 33. However, 25% of the CIN 2/3 lesions were not detected by these four HPV tests. We suggest that HPV testing could usefully augment but not replace conventional cytology. These results should stimulate a much larger randomised trial to assess the impact of these improved CIN 2/3 detection rates on the subsequent incidence of invasive cancer.