We report here the identification of two distinct human cDNAs, called VNN1 and VNN2, related to the recently described mouse Vanin-1 molecule involved in lymphocyte migration (M. Aurrand-Lionset al.,1996,Immunity5: 391–405). Tissue distribution of the expression of these two human Vanin-like genes is differential. Since Vanin-1 shares significant homologies with human biotinidase (BTD), we describe here a new family of related genes including at least four members: mouse Vanin-1, VNN1, VNN2, and BTD. We have mapped the murine locus encompassing the Vanin-1 gene on mouse chromosome 10 in position A2B1. The two human Vanin-like genes are closely linked, since they were found on the same YAC clone and colocalized on human chromosome 6q23–q24 known to contain several genetic alterations linked to the progression of metastatic human cancers.