Updated project metadata. Upregulation of the proto-oncogene TCL1A is causally implicated in various B- and T-cell malignancies. High-level TCL1A correlates with aggressive disease features and inferior clinical outcomes. However, molecular and cell-biological consequences of TCL1A dysregulation are not fully elucidated. Here, we identify CDC20 and other molecules of the safeguarding cell cycle checkpoints as novel TCL1A-interactors. In different model systems of B-cell leukemia/lymphoma, TCL1A overexpression accelerated cell cycle transition, impaired apoptotic damage responses in association with pronounced chromosome mis-segregation and caused cellular aneuploidy. In primary CLL samples, low CDC20 expression correlated with high expression of TCL1A and more aggressive disease characteristics. In line, a low CDC20 expression was a marker for reduced progression-free survival in CLL patients. Finally, knockdown of CDC20 in TCL1A-initiated murine lymphomas promoted chromosome disbalances and leukemia outgrowth. Overall, we discovered a cell-cycle associated effect of TCL1A by interfering with a proficient cell cycle transition. This adds to our concept of TCL1A’s transforming impact by targeting genome stability.