Wnt10b is a member of the Wnt ligand gene family that encodes for secreted proteins, which activate the ancient and highly conserved Wnt signalling cascade. The Wnt pathway has been shown to be essential for embryonic development, tissue integrity, and stem cell activity, but if deregulated, also causes disease such as cancer. Although the 19 different Wnt ligands found in both human and mouse can activate several branches of the Wnt pathway, WNT10B specifically activates canonical Wnt/β-catenin signalling and thus triggers β-catenin/LEF/TCF-mediated transcriptional programs. In this review, we highlight the unique functions of WNT10B and mechanisms of how WNT10B acts in the immune system, mammary gland, adipose tissue, bone and skin. In these organs, WNT10B has been well established to be involved in signalling networks controlling stemness, pluripotency and cell fate decisions. Deregulation of these processes causes diseases such as breast cancer, obesity and osteoporosis. Compelling evidence suggests that WNT10B is a valuable candidate for the development of therapeutic regimens for human diseases.