γδ T cells, including Vδ1 and Vδ2 T cells, can recognize tumor-associated ligands neglected by conventional αβ T cells in a MHC-independent manner. Little is known regarding the anticancer potential and the possibility to isolate and expand Vδ1 T cells to therapeutically relevant numbers. In this study, we have detected low frequencies of Vδ1 T cells among tumor-infiltrating lymphocyte (TIL) products for adoptive cell transfer generated from melanoma metastases. An increased frequency of Vδ1 T cells was found among the cell products from patients with an advanced disease stage. Vδ1 T cells displayed in vitro antitumor activities and sufficient proliferative potential to generate over 1 × 10(9) cells using current protocols for T cell transfer. Infusion of Vδ1 T cells together with high numbers of αβ TILs in a clinical trial was safe and well tolerated. These data suggest that Vδ1 T cells should be further scrutinized as a potentially useful tool for the treatment of patients with metastatic melanoma.