BACKGROUND. The frequently cited number of 50 million annual Papanicolaou cervical screening (Pap) tests performed in the US was based on the National Health Interview Survey (NHIS) of the 1980s. Since then, monumental changes have occurred. More change will soon follow when primary human papilloma virus (HPV) testing and/or HPV vaccine delivery are fully accepted and implemented. The objectives of this study were 1) to estimate the total annual Pap tests performed in the US based on recent NHIS surveys, and 2) to estimate the potential change in the total annual Pap volume produced by changing demographics, reduced screening frequency, HPV testing, and the HPV vaccine. METHODS. In the NHIS 2000 and NHIS 2005, women were asked to report the frequency of their Pap tests for the 6 years prior to the interview and to report whether they had abnormal findings. The authors analyzed the survey respondents answers to these questions by using SAS Survey Procedures (SAS Institute, NC). The results were stratified by age, and the total national volume was then extrapolated from a similarly stratified 2000 US census. The projected increase of total Pap tests for the next 25 years was determined by using the projected census data. Potential reductions of Pap tests performed secondarily to HPV testing of women >30 years old and of HPV vaccination were also determined. RESULTS. Based on NHIS 2000 and NHIS 2005, 66 million (95% CI, 65-68) and 65 million (95% CI, 64-67) Pap tests were performed in the US, respectively. Had HPV testing been performed in women older than 30 years who had both negative HPV and negative 3-year Pap tests, then 30% (95% CI, 29-32%) of Pap tests would not have been performed. If both HPV testing and vaccination are performed, the total number of Pap tests performed annually is predicted to be reduced by 43% (95% CI, 35-38%). CONCLUSIONS. Therefore, despite an expected increase in the population of women eligible for Pap tests, the total number will likely decrease substantially in the future. This, in turn, will decrease the demand for a traditionally trained cytotechnology workforce. © 2007 American Cancer Society.