After a two-year planning and development process, the American Cancer Society (ACS) announced methods and procedures for the development of cancer screening guidelines. The update of the guideline process was motivated by criticism that ACS guidelines were insufficiently transparent with respect to process and decision making; concerns about potential conflicts of interest when specialists serve on the guidelines committee; the lack of clarity regarding differences in cancer screening guidelines written by different organizations, even when they are based on the same evidence; and the availability of two new reports issued by the Institute of Medicine (IOM) setting forth new standards for developing more trustworthy clinical practice guidelines and conducting systematic evidence reviews. Because the ACS is an important source of guidance about cancer screening for both health care practitioners and the general public, it was important to revise the methodology to address these concerns and independent standards to insure a more transparent, consistent, and rigorous process for developing and communicating guidelines. The new ACS methods align with the IOM principles for trustworthy clinical guideline development by: creating a single generalist group for writing the guidelines; commissioning independent systematic evidence reviews; and clearly articulating the benefits, limitations, and harms associated with a screening test(s). This new process should ensure that ACS cancer screening guidelines will continue to be a trustworthy source of information for both health care practitioners and the general public to guide clinical practice, personal choice, and public policy about cancer screening. Several examples of differences in current recommendations issued by different organizations will be discussed.