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The objectives of this study were to compare the sensitivity of colposcopically directed biopsy (biopsy of cervical quadrants with colposcopic impressions of human papillomavirus, cervical intraepithelial neoplasia [CIN], or cancer) for CIN 3 or cancer (CIN 3+) among physicians and to estimate the increase in yield of CIN 3+ per colposcopy associated with "random" biopsies and/or endocervical curettage (ECC).Two studies in which 7 physicians performed 1,383 colposcopic examinations on women with abnormal cervical cytology were reviewed. At colposcopy, the cervix was divided into quadrants by lines from the 12- to the 6-o'clock and from the 3- to the 9-o'clock positions. Each quadrant was assigned a colposcopic impression of normal, human papillomavirus or CIN 1, CIN 2 or CIN 3, or cancer. Each quadrant had biopsy of colposcopically detected lesions or "random" biopsy at the squamocolumnar junction if the colposcopic impression was normal. Lastly, ECC was obtained.Among the physicians, the sensitivity of colposcopically directed biopsy for CIN 3+ varied from 28.6% to 92.9% (p < .001). With logistic regression, the sensitivity of colposcopically directed biopsy for CIN 3+ increased as the number of cervical quadrants with CIN 3+ increased (p < .001); once corrected for the number of quadrants with CIN 3+, differences between the physician's sensitivities remained significant (p = .01). For 6 of 7 physicians, the yield of CIN 3+ per colposcopy was greater when colposcopically directed biopsy was augmented by up to 4 "random" biopsies plus ECC (p = .03 to p < .001).The sensitivity of colposcopy for CIN 3+ varies widely. Performing up to 4 "random" biopsies plus ECC increases the yield of CIN 3+.