Bmi1 is a member of the polycomb group (PcG) proteins. PcG proteins form multiprotein complexes that function as transcriptional repressors. Several lines of evidence implicate Bmi1 in tumorigenesis. Firstly, Bmi1 cooperates with c-Myc in the generation of lymphomas in double transgenic mice. Secondly, Bmi1 blocks senescence and immortalizes mouse embryo fibroblasts, although not human fibroblasts, and in combination with an activated H-ras gene leads to neoplastic transformation. Thirdly, the BMI1 gene is amplified in certain mantle cell lymphomas and is overexpressed in a subset of non-small cell lung cancer, colorectal carcinomas, multiple myelomas and medulloblastomas, but not glioblastomas. Fourthly, the transformation of human hematopoietic progenitor cells by the oncogenic fusion protein E2a-Pbx1 requires Bmi1. Based on a list of genes differentially expressed in a mouse model of metastatic prostate cancer on a wild-type and bmi1-deficient genetic background, a gene signature was recently identified that may predict response to therapy and survival in multiple types of cancer.