Ikaros is the founding member of a family of zinc finger transcription factors whose function during early hematopoietic development is required for differentiation into the three major hematopoietic lineages. Ikaros deletions have been described in human malignancies, particularly precursor B-cell leukemia. Deletions of this transcription factor appear to mediate leukemogenesis, although the exact mechanism is unclear. This article reviews the structure and function of Ikaros proteins in chromatin remodeling and gene expression as well as the current knowledge of Ikaros deletions in human malignancies. A new proteomic platform, mass cytometry, is introduced which allows measurements of greater than 30 parameters at the single-cell level and should thus provide a greater level of detail to unravel the mechanistic consequences of Ikaros dysfunction in leukemia.