The thymus is a central lymphoid organ critical for the development and maintenance of an effective peripheral T-cell repertoire. Most important, it provides a specialized environment for the selection of rearranged clones that will function appropriately in the adaptive immune response. Thymic involution has been observed in several model systems; including graft-versus-host disease, aging, viral infection, and tumor development, however, the precise mechanisms involved in this phenomenon remain poorly defined. Here, we review some of our results related to the studies of the cell-mediated immunity in a mammary tumor model; more specifically, those related to the tumor-induced impaired T-cell development and thymic involution. Collectively, the understanding of the mechanisms and pathways associated with the tumor-induced thymic involution is essential for the development of innovative and safe therapies to fight against the immune suppression caused by the tumor development.