Within living organisms, stem cells respond to various cues, including to niche signals and growth factors. Niche signals originate from the stem cell's microenvironment and promote the undifferentiated state by preventing differentiation, allowing for stem cell self-renewal. On the other hand, growth factors promote stem cell growth and proliferation, while their sources comprise of a systemic input reflecting the animal's nutritional and metabolic status, and a localized, homeostatic feedback signal from the tissue that the stem cells serve. That homeostatic signal prevents unnecessary stem cell proliferation when the corresponding differentiated tissues already have optimal cell contents. Here, we recapitulate progresses made in our understanding of in vivo stem cell regulation, largely using simple models, and draw the conclusion that 2 types of stem cell deregulations can provoke the formation of benign tumors. Namely, constitutive niche signaling promotes the formation of undifferentiated "stem cell" tumors, while defective homeostatic signaling leads to the formation of differentiated tumors. Finally, we provide evidence that these general principles may be conserved in mammals and as such, may underlie benign tumor formation in humans, while benign tumors can evolve into cancer.