In murine models of breast cancer, melanoma, and lymphoma brain metastases, we confirmed that KLK6 overexpression was linked to the implantation of cancer cells in the brain.<h4>Conclusion</h4>KLK6 overexpression is linked to brain localizations whatever the cancer type, which provides new perspectives for the development of anti-KLK6 therapeutic strategies, pending specific cancer cell targeting to avoid cytotoxicity on normal brain cells. This evidence concerns the gene KLK6 and melanoma.