We describe here the function of a molecule known as the stem loop binding protein, SLBP, in transformation in vivo and in vitro. SLBP was an important and essential component of the gene signature of early transformation in vivo when studying neoplasia in the human vulva. SLBP induction occurred early in transformation concurrent with activation of HELLS and CDT1, DNA damage repair protein RAD51AP1, an Xist repair pathway adapter protein UHRF1, and epigenetic enzymes EZH2 and DNMT1. SLBP was activated by mutation of MRE11A or H2AX, indicating its relative position in biological functions relevant to the relationship between DNA damage and transformation. Importantly, SLBP expression was silenced in ATM knockout cells. SLBP induction during transformation and temporal dynamics in neoplasia in vivo indicate an important transcriptional function for SLBP in transformation.