A rapid prescreening or rapid rescreening method for quality assurance in cervical cytology has been used in Europe and in Canada but has not been accepted in the United States. The rapid prescreen method was tested in a cytology laboratory that serves an academic medical center with a high-risk population for cervical cancer. For a period of 3 months, a tray of 20 sequentially numbered Surepath™ liquid-based preparations, randomly selected from the cervical cytology daily workload, were each prescreened in a random fashion for 1 minute. Experienced cytotechnologists performed the rapid prescreen. Results were recorded as negative, further review needed, or epithelial cell abnormality, category specified. The 20 cervical cytology preparations were then replaced in their same position in the daily workload for routine screening performed by another cytotechnologist. Final interpretation was by a cytopathologist as requested or required by Clinical Laboratory Improvement Amendments of 1988. The rapid prescreen data was tabulated and compared with data for a similar time period using the laboratory's normal quality assurance program. Seven hundred and twelve cases underwent rapid prescreen. Six hundred and forty-two were interpreted as negative. Twenty-six cases were interpreted as low-grade squamous intraepithelial lesion (LGSIL) or higher. Forty-four cases were classified as needing further review. For the 642 negative cases by rapid prescreening, routine screening reported 537 as negative and 105 as either abnormal or needed cytopathologist review. The error rate for the rapid prescreen is 50 of 712 (7.0%); for LGSIL and above 19 of 712 (2.6%). Of the 105 abnormal cases or those submitted for cytopathologist review, 31 were interpreted as atypical squamous cells of undermined significance (ASCUS), 41 cases as reactive/repair, 17 as LGSIL, 4 as unsatisfactory, 1 as atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H), 8 as the presence of endometrial cells in a women aged >40, 1 as malignant melanoma, and 2 as within normal limits with the presence of Actinomyces. The laboratory's routine quality assurance program selects cases, 10% of initially interpreted negative cases plus any gynecologic cytology on patients with a prior abnormal cervical cytology, or history of cervical epithelial cell abnormality. This quality assurance program averages 29% of cases, 4,045 of a total of 13,767, in 2008. Thirty-seven (0.9%) cases were detected in this rescreen (ASCUS, 16 cases; LGSIL, 13 cases; 1 high-grade squamous intraepithelial lesion; 4 ASC-H; and 3 atypical glandular cells of undetermined significance). Eliminating ASCUS cases, eight significant cases were detected, with an error rate of 0.2%. In this cytology laboratory, the rapid prescreen did not prove as reliable as routine quality assurance program for cervical cytology cases.