In this study, we provide formal demonstration that CDK12 is a primary oncogenic driver in the normal mammary gland showing that CDK12 overexpression per se: (i) causes the appearance of transformed phenotypes in vitro; (ii) drives the early appearance of preneoplastic lesions and, with a longer latency, the emergence of multiple and multifocal spontaneous infiltrating tumors in vivo; (iii) accelerates in vivo tumorigenesis caused by exposure to the chemical carcinogen, DMBA, and enhances tumor progression and spontaneous distant metastasis in oncogene-driven mouse breast tumor models. Here, CDK12 is linked to neoplasm.