The endometrium is recognized for its remarkable regenerative and remodeling capacity. Every month this hormonally regulated organ undergoes cycles of growth (from 0.5–2 to 7 mm), regression and shedding of two-third of the tissue, leading to its monthly renewal that occurs ∼400 times in a woman's reproductive lifetime. Several groups have suggested the existence of a human endometrial somatic stem cell (SSC) population located around the spiral arterioles of the basalis. Different groups have isolated, identified and characterized putative endometrial SSC populations in human endometrium based on the general features of undifferentiated cells, such as slow cycling detected using the 5-bromo-2-deoxyuridine technique or identification of a side population using the Hoechst efflux dye technique. Nevertheless, specific markers to isolate these endometrial SSC have not yet been consistently elucidated. Accumulated evidence based on lineage tracing studies indicates that a surface protein named Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a marker that can identify SSC in several tissues such as small intestine mucosa (endodermal origin), hair follicles (ectodermal origin) or mature kidney nephrons (mesodermal origin). This protein plays a crucial role in the Wnt/β-catenin signaling system by acting on the self-renewal and maintenance of the SSC population. In this work, we present novel data suggestive of Lgr5 as a putative human endometrial SSC marker, and since this is a mesoderm-derived tissue, these findings reinforce the concept that Lgr5 can be considered a universal SSC marker.