Herein, we demonstrate that: (1) elevated levels of Spy1 is a transforming event, (2) Spy1-mediated transformation relies on the activation of Cdk1 and may mediate an inhibition of the pro-apoptotic regulator FOXO1, (3) levels of Spy1 protein are highly elevated in aggressive human breast cancers and (4) downregulation of Spy1 can significantly inhibit breast cancer cell growth. This evidence concerns the gene SPDYA and breast cancer.