Mutations in RAS genes are very rare in human breast cancers, but the Ras signaling pathway is hyperactivated in half of these tumors. Now, Karen Cichowski and colleagues identify a new driver of Ras pathway activation in breast cancer and show that it functions as a tumor and metastasis suppressor (Cancer Cell 24, 365–378, 2013). The authors initially identified RASAL2 in a cell-based screen for Ras GTPase-activating proteins with growth suppressive activity. By searching publicly available databases, they found that the catalytic domain of RASAL2 is targeted by mutations in human breast cancers and other human tumor types. Mouse xenograft studies showed that RASAL2 expression suppressed the growth of tumors derived from a RASAL2-deficient breast cancer cell line, and short hairpin RNA (shRNA)-mediated suppression of endogenous RASAL2 in a breast cancer cell line promoted tumor growth. The authors generated genetically engineered mice that lack Rasal2 and found that, although the Rasal2-deficient mice did not develop mammary tumors, loss of Rasal2 increased the number of metastases in an engineered mouse model of mammary tumorigenesis. This work identifies a new mechanism by which Ras becomes activated in breast cancer.