IntroductionPhiladelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL) is a high risk form of ALL associated with dismal outcomes in the pre‐tyrosine kinase inhibitor (TKI) era. Addition of a TKI to chemotherapy improves outcomes. Therefore, testing for the presence of the Philadelphia chromosome by at least two methods at the time of diagnosis is critical. Diagnostic testing may include karyotype, fluorescent in situ hybridisation (FISH), and RT‐PCR for the BCR::ABL1 transcript. The significance of low‐level BCR::ABL1 transcript by RT‐PCR in the absence of the Philadelphia chromosome on karyotype or by FISH is unknown.MethodsThis is a retrospective review of children diagnosed with acute leukemia at our institution from 2010 to 2020. Those positive for the BCR::ABL1 transcript by qualitative RT‐PCR, and negative for t(9;22) by karyotype or FISH were analyzed for demographics, cytogenetic and molecular features at diagnosis and relapse, treatment and outcomes. The Kaplan–Meier method was used to estimate event‐free and overall survival.ResultsForty‐seven of 306 (15%) patients with Ph‐ ALL had low‐level BCR::ABL1 detected by RT‐PCR. Most (77%) had B‐cell ALL. The e1a2 transcript was detected most frequently, in 43 (91%) patients. BCR::ABL1 was quantifiable in 12/43 (28%) patients, with a median of 0.0008% (range 0.0003–0.095%). Seven patients (15%) relapsed. No patient with low‐level BCR::ABL1 at diagnosis developed Ph + ALL at relapse. There was no difference in 5‐year event‐free (77% versus 81%, p = 0.407) or overall survival (86% versus 91%, p = 0.3) between children with low‐level BCR::ABL1 (n = 47) and those without (n = 259).ConclusionBCR::ABL1 low‐level positivity in children with newly diagnosed Ph‐ ALL is a relatively common finding and did not adversely affect outcome for patients treated using a contemporary risk‐adapted approach.