CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07-5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children's motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS's total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children's motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis' tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia.