: Cytogenetic biomarkers are commonly used in assessing the impact of environmental, demographic, life style exposures, occupational, and medical factors on genomic instability. The acquisition of genomic instability, a condition that predisposes a cell to accumulate stable genome mutations represents an early step in the process of carcinogenesis. Micronucleus (MN) testing serves as an important biomarker in assessing DNA damage defects in mitosis. Cytokinesis Block Micronucleus (CBMN) cytome assay is a multi- endpoint assay that not only assesses DNA damage endpoints in the form of micronucleus (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDS) but also other cytotoxic events such as necrosis, apoptosis, and cell proliferation are measured. In this brief review, we would like to discuss the evolution of the CBMN cytome assay as an effective biomarker for risk prediction, screening, and diagnosis in cancer..