Abstract BACKGROUND Central nervous system (CNS) tumors are the most common solid cancer in children, second only to leukaemia. METHODS We conducted a retrospective epidemiological study of primary CNS tumors diagnosed in children up to 16 years of age between 2012 and 2023, in order to estimate the incidence in a regional cohort of 1,2 million inhabitants (Northeastern Italy). Only primitive lesions were enrolled, relapses were excluded. RESULTS Over a period of twelve years, 100 new diagnoses were made (44% Female, 56% Male) with a mean age of 8,92 years (range 0-16 years) at time of onset. In terms of location, we recorded an equal number of supratentorial and subtentorial diagnoses (50% vs 50%). A time-series analysis was performed to verify possible variations in the incidence rate of brain tumors over years, and no significant change was described (R2 0.301, p=0.06). However, after 2017 a significant increase was noted (R2 0.725, p=0.015), as the incidence of new diagnosis quite doubled, from 3.16 in 2018 (95%CI 3.15-3.17) to 5.59 in 2023 (95%CI 5.57-5,61). Data were therefore divided in two groups: 2012-2017 (group 1), and 2018-2023 (group 2). There were no differences in terms of gender or age. The number of low-grade (LG) and high-grade (HG) diagnosis were compared: HG tumors, including high grade glioma, ependymoma and medulloblastoma, were significantly higher in the group 2 than group 1 (27/50, 54% vs 6/43, 14%, p<0.001). CONCLUSIONS In childhood, CNS tumors incidence has been fairly stable in the last twelve years in our regional cohort, but a recent concern of an increased rate of high-grade diseases emerged according to our data. In case of a confirmation of this trend, further analysis will be required in order to understand the reason.