<p>A significant lack of participation in colorectal cancer (CRC) screening programs in the United States limits the impact of screening to reduce morbidity and mortality. Recently a group of experts in CRC screening defined the Guiding Principles for Noninvasive Testing (GPNIT). GPNIT pathway is intended to serve as a step by step guide for study design to ultimately lead to implementation and integration of a potentially clinically appropriate CRC screening test. Multi-target stool DNA (MT-sDNA) test usage for CRC screening has increased significantly recently in the United States. Here, the key studies in the development of MT-sDNA as an emerging CRC screening test are placed in context of the GPNIT pathway for CRC screening test development. This case study is meant to be instructive for future test development in CRC screening to achieve ultimately clinically relevant future tests and improve the efficacy of CRC screening.</p>