CD8(+)CD62L(+) T cells have been shown to play pivotal roles in anti-viral immunity, chronic myeloid leukemia and renal cell carcinoma. Recently, CD8(+)CD62L(+) T cells from naïve mice (nCD8(+)CD62L(+) T cells) have shown superior anti-tumor properties in melanoma-bearing mice. Considering that antigen-specific memory T cells have shown to possess more potent immunity than non-specific memory T cells, we hypothesized that CD8(+)CD62L(+) T cells from tumor-bearing individuals (mCD8(+)CD62L(+) T cells) might have superior anti-tumor effect than nCD8(+)CD62L(+) T cells. Therefore, we investigated phenotypes, functions and the in vivo distribution of mCD8(+)CD62L(+) T cells in tumor-bearing mice. We found that, while keeping the features of central memory T cells, the frequency of mCD8(+)CD62L(+) T cell in the spleen of tumor-bearing mice was significantly higher than that the one of nCD8(+)CD62L(+) T cell in naive mice. Moreover, we demonstrated that mCD8(+)CD62L(+) T cells had higher proliferation rate and IFN-γ production than nCD8(+)CD62L(+) T cells, in vitro. We performed adoptive transfer of mCD8(+)CD62L(+) T cells into melanoma-bearing mice and tracked them in spleen, lymph nodes and in melanoma tissues. Our results show that mCD8(+)CD62L(+) T cells had stronger in vivo anti-tumoral activity than nCD8(+)CD62L(+) T cells. This study highlights the therapeutic potential of mCD8(+)CD62L(+) T cells in the immunotherapy of melanoma and possibly other tumors.