This study identifies a long-lived human memory T-cell subset with stem cell-like properties. These cells, characterized by the expression of CD95 and IL-2Rβ, are found within the CD45RO+, CCR7+, CD45RA+, CD62L+, CD27+, CD28+, and IL-7Rα+ T-cell compartment, which is typically associated with naive T cells. However, they exhibit enhanced self-renewal and multipotency, capable of differentiating into central memory, effector memory, and effector T cells. These cells are specific for multiple viral and self-tumor antigens and display superior proliferative capacity, reconstitutive ability in immunodeficient hosts, and anti-tumor responses in a humanized mouse model. The identification of this stem cell-like memory T-cell population has significant implications for the design of vaccines and T-cell therapies.This study identifies a long-lived human memory T-cell subset with stem cell-like properties. These cells, characterized by the expression of CD95 and IL-2Rβ, are found within the CD45RO+, CCR7+, CD45RA+, CD62L+, CD27+, CD28+, and IL-7Rα+ T-cell compartment, which is typically associated with naive T cells. However, they exhibit enhanced self-renewal and multipotency, capable of differentiating into central memory, effector memory, and effector T cells. These cells are specific for multiple viral and self-tumor antigens and display superior proliferative capacity, reconstitutive ability in immunodeficient hosts, and anti-tumor responses in a humanized mouse model. The identification of this stem cell-like memory T-cell population has significant implications for the design of vaccines and T-cell therapies.