Deregulated over-expression of the transcription factor MYC is implicated in the development and malignant progression of most (~70%) human tumours. MYC drives cell growth and proliferation but also, at high levels, promotes apoptosis. We have found that MNT, a MYC-related transcriptional repressor, plays a vital role in both B lymphopoiesis and lymphomagenesis, primarily by suppressing MYC-driven BIM-mediated apoptosis. In Eu-Myc mice, which model the MYC/IGHchromosome translocation in Burkitt’s lymphoma, homozygous Mnt deletion markedly lowered premalignant B lymphoid populations and greatly reduced lymphomagenesis. Strikingly, when Mnt was deleted within established Eu-Myc lymphoma cells transplanted into normal immunocompetent mice, survival of transplant recipients was significantly extended. The dependency of MYC-driven lymphomas on MNT for continued growth indicates that drugs inhibiting MNT could significantly boost therapy of MYC-driven tumours.