Using proviral tagging in combination with in vitro selection for invasiveness, we have identified a gene, designated Tiam. 7, that affects invasion. In the selected invasive T lymphoma variants, proviral insertions were found within codlng exons of the Tiam-7 gene, resulting in both truncated S-end and 3’-end transcripts that give rise to N-and C-terminal Tlam-1 protein fragments. In one invasive variant, ampllfication of the Tiam-7 locus was observed with concomitant increase in the amount of normal Tiam-1 protein. Cell clones that were invasive in vitro produced experimental metastases in nude mice, and transfection of truncated Tiam-f cDNAs into noninvaslve cells made these cells invasive. The predicted Tiam-1 protein harbors a Dbl-and Pleckstrin-homologous domain, which it shares with GDP-GTP exchangers for Rho-like proteins that have been implicated in cytoskeletal organization.