Numerous studies have highlighted the existence of two distinct stem cell populations in the mouse intestine, one located at the crypt base and marked by expression of Lgr5 and another located at the +4 position relative to the crypt base and marked by expression of Bmi1. Jonathan Epstein and colleagues now show that these two stem cell populations share a bidirectional lineage relationship (Science, published online 10 November 2011; doi:10.1126/science.1213214). The authors identified the homeobox gene Hopx as a new marker of stem cells at the +4 position. Using lineage tracing, they showed that these Hopx-expressing cells can give rise to all cell types along the crypt-villus axis, including Lgr5-positive cells at the crypt base. In reciprocal lineage tracing studies, they found that Lgr5-expressing cells can give rise to Hopx-positive cells at the +4 position, indicating that these two stem cell populations can interconvert. The dynamics of the labeling studies indicate that the Hopx-positive cells represent a more quiescent stem cell population than the more rapidly cycling Lgr5-positive cells. These findings help reconcile prior controversies in the field and provide insights into the relationship between these two stem cell populations.