The conducted a multicentre retrospective study with chart and pathol. review of all cases of MPAL/ALAL diagnosed and treated at University Hospital Southampton (UHS) and Sheffield Children's Hospital (SCH), UK from the year 2015 until 2020.A total of three children with bilineal and biphenotypic acute leukemia and a predominant monocytic component (UHS, one; SCH, two) were enrolled.Initial screening performed using two tubes for both myeloid and lymphoid lineages; eight surface markers: CD33 (Becton Dickinson [BD], Franklin Lakes, NJ, USA; 345800), CD34 (BD; 345803), CD117 (BD; 339217), CD45 (BD; 641417), human leukocyte antigen-DR isotype (HLA- DR; BD; 655874), CD10 (BD; 341112), CD19 (BD; 345791) and CD7 (BD; 642916) and five cytoplasmic markers: IgM (Dako, Glostrup, Denmark; R511101), terminal deoxynucleotidyl transferase (Bio-Rad, Pleasanton, CA, USA; OBT0012), CD3 (BD; 345766), CD79a (Dako; R7159) and myeloperoxidase (MPO; BD; 333138).MFC MRD identifies leukemia cells down to 0 01% as a min. in ALL and when > 4 million cells are measured for ALL, MFC MRD is considered as sensitive as polymerase chain reaction-based methods.Biphenotypic and bilineal ALAL is extremely rare in children with associated diagnostic and therapeutic challenges.