Forkhead box P3 (Foxp3) is an important transcription factor that belongs to the forkhead/winged-helix family of transcriptional regulators. Foxp3 has been extensively studied over the past 13 years as a master regulator of transcription in a specific T-cell type, CD4(+) regulatory T cells (Treg), both in humans and in mice. Compelling data characterize Foxp3 as critically important and necessary for the development and the differentiation of Treg. It has been considered initially as the only specific marker for Treg. However, recent work has proposed that Foxp3 can be expressed by other types of lymphoid cells or myeloid cells and also by some non-hematopoietic cells such as epithelial cells. It remains controversial about the expression of Foxp3 in cells other than Treg, but understanding the potential expression and function of this master regulator in different cell subsets could have a wide range of implications for immune tolerance and several pathologies including autoimmune disorders and immune responses to cancer.