An E3B1/Abi2/Argbp1/NESH protein family has recently emerged from analysis of the sequence and structural similarities. These are adaptor proteins possessing homeobox homology domain, proline rich region and Src-homology 3 (SH3) domain that interact with Abl-family tyrosine kinases. Some of the members of this family are involved in cytoskeletal reorganization that plays important roles in membrane-ruffling, lamellipodia formation and cell migration. Furthermore, it seems likely that this family may also regulate cancer development through modulation of the oncogenic Abl kinase. The knowledge of this status is helpful in thinking of the regulatory mechanisms to cell metastasis and to malignant transformation of cancer. We discuss how these interesting molecules work and consider their involvement in cancer.