The cancer stem cell hypothesis has recently evolved from an increasing body of evidence suggesting that in some cancers a small population of tumor cells with stem cell-like properties represents a critical component that dictates the malignant behavior of a given tumor. These observations challenge classical cancer biology and its theory, that tumor growth is mainly based on genomic alterations followed by modulation of cell cycle pathways, which finally result in uncontrolled clonal proliferation. Over the last few years, much progress in the field of tumor stem cells has been achieved in non-endocrine malignancies. In this review, we summarize the existing evidence regarding the tumor stem cell concept for tumor pathophysiology in general and highlight current models that have the potential to further impact research on endocrine tumors.