Minimal residual disease (MRD) as a tool to monitor response to therapy is both a criterion for detailed risk stratification and an independent prognostic factor in childhood acute lymphoblastic leukemia (ALL). Immunological assays particularly flow cytometry (FC) are priority methods in MRD monitoring. Multicolor flow cytometry makes it possible to most fully characterize the immunophenotype of tumor B lymphoblasts and reveal leukemia-associated immunophenotypes not only according to the CD58 and CD38 antigens but also as an additional criterion of aberrancy. This allows you to identify and select individual criteria for further monitoring of minimal residual disease for each patient with ALL. The aim of this chapter is to compare immunophenotyping features of normal B-cell precursors and B-lymphoblasts in acute leukemia and to show possibilities of use of a leukemiaassociated immunophenotype in monitoring of the MRD.