Objective: To report a pediatric case of pegfilgrastim-induced hyperleukocytosis. Case Summary: A 3-year-old boy with medulloblastoma therapy presented with white blood cell (WBC) count 0.1 × 103/μL and absolute neutrophil count (ANC) 0.014 × 103/μL on day 27 following a course of induction chemotherapy. The patient received pegfilgrastim 200 μg/kg the following day. On his return 6 days later for the next planned course of chemotherapy, hyperleukocytosis was determined, with WBC 149 × 103/μL and ANC 110 × 103/μL (“neutrophil overshoot”). No sources of the elevated WBC count other than administration of pegfilgrastim (eg, steroids, antiepileptics, infection) were present. Chemotherapy was delayed until the WBC count had fallen to 35.2 × 103/μL (ANC 28.9 × 103/μL). No sequelae from this adverse effect occurred. Discussion: Pegfilgrastim has unique saturable neutrophil receptor-mediated clearance, the ability for self-regulation. Due to this clearance mechanism, hyperleukocytosis associated with pegfilgrastim use is uncommon in adults and has not been previously reported in pediatrics. The pegfilgrastim dose in children is under investigation; however, 100–110 μg/kg has been effective and safe in this population. Use of the Naranjo probability scale suggested that pegfilgrastim was the probable cause of hyperleukocytosis in our patient. Conclusions: Pegfilgrastim 200 μg/kg, in excess of the 100 μg/kg dose used in limited pediatric clinical trials, appeared to exceed saturable neutrophil receptor-mediated clearance. The inability of this mechanism to self-regulate neutrophil counts in the normal range led to neutrophil overshoot. Routine pediatric use of the pegylated dosage form of G-CSF should await further published clinical trials to validate a safe and effective dose.