We have identified that StarD10, a member of the START protein family, is overexpressed in both mouse and human breast tumors. StarD10 was initially discovered on the basis of its cross-reactivity with a phosphoserine-specific antibody in mammary tumors from Neu/ErbB2 transgenic mice and subsequently isolated from SKBR3 human breast carcinoma cells using a multistep biochemical purification strategy. We have shown that StarD10 is capable of binding lipids. StarD10 was found to be overexpressed in 35% of primary breast carcinomas and 64% of human breast cancer cell lines, correlating with their ErbB2/Her2 status. Coexpression of StarD10 with ErbB1/epidermal growth factor receptor in murine fibroblasts enhanced anchorage-independent growth in soft agar, providing evidence for functional cooperation between StarD10 and ErbB receptor signaling. Taken together, these data suggest that overexpression of this lipid-binding protein contributes to breast oncogenesis.