morphologically and immunophenotypically resemble B-lineage and T-lineage precursor cells. These neoplasms may present predominantly as a leukemic process, with extensive involvement of the bone marrow and peripheral blood or may be limited to tissue infiltration, with absent or only limited (less than 25%) bone marrow involvement. Philadelphia-like (Ph-like) B-cell ALL is a high-risk subtype of B-cell ALL that shares a gene expression profile with Ph-positive ALL, but without a BCR::ABL1 fusion. A subgroup of these patients have fusions or rearrangements involving genes such as ABL1, ABL2, PDGFRβ, JAK2, and EPOR, some of which are potentially sensitive to tyrosine kinase inhibitors (TKIs). Prompt identification of these genetic aberrations are important for prognostication and treatment decisions. The presence of Ph-like defect in patients with ALL is a new marker of high risk subtype associated with poor outcome and frequent relapse. This review summarizes recent modalities of diagnosis of Ph-like ALL. Conclusion: The diagnosis of Ph-like ALL is challenging, however it carries predictive and prognostic implications that help to better define the patient’s risk and to personalize the treatment approach based on the presence of targetable mutations. Gene expression profiling (GEP) is cumbersome to use in daily clinical practice. Other methods, relying on reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), or combination of immune-phenotyping and DNA-sequencing have been used. Identifying sensitive and specific algorithms will be very helpful to identify and treat Ph-like ALL in daily clinical practice