Intestinal epithelium is a rapidly cycling tissue, always renewing every 4–5 days under normal conditions, which is maintained by intestinal stem cells (ISCs). Using the fluorescence labelling trace, ISCs can be divided into two different types: active intestinal stem cells (A-ISCs) located in bottom of the intestinal crypt and the quiescent intestinal stem cells (Q-ISCs) in the +4 position of the crypt. There is a complex signal regulation net between the ISCs and other intestinal cells, such as Wnt and Notch pathways. ISCs have an intimate relationship with the colorectal cancer (CRC). However, a deficiency of stem cells markers severely limits research on the biological characteristics of ISCs. We have reviewed several ISCs markers, including Lgr5, PHLDA1, Bmi1 and Lrig1. These markers have widely different biological functions, but also have a close relationship with cancers, especially CRC. Our hypothesis concerns the reasons for ISCs having two distinct types and why endless ISCs markers have emerged.