New cervical cancer prevention strategies are arising from rapidly improving insight into human papillomavirus (HPV) natural history and cervical carcinogenesis, challenging the conventional roles of cytology and colposcopically directed biopsy as the reference standards of screening and diagnosis, respectively. HPV testing has high sensitivity but mediocre specificity and positive predictive value, making the role of colposcopy for the accurate identification of patients requiring treatment even more important. We believe that deficiencies of the colposcopically guided biopsy must be addressed, in particular, the inaccuracy of biopsy placement leading to low sensitivity for detection of CIN3. This opinion outlines our concerns and summarizes new data, suggesting possible steps that may lead to improvement in colposcopic accuracy.