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© 2017 European Paediatric Neurology Society Background Upper limb (UL) function in children with unilateral cerebral palsy (CP) vary largely depending on presumed timing, location and extent of brain lesions. These factors might exhibit a complex interaction and the combined prognostic value warrants further investigation. This study aimed to map lesion location and extent and assessed whether these differ according to presumed lesion timing and to determine the impact of structural brain damage on UL function within different lesion timing groups. Materials and methods Seventy-three children with unilateral CP (mean age 10 years 2 months) were classified according to lesion timing: malformations (N = 2), periventricular white matter (PWM, N = 42) and cortical and deep grey matter (CDGM, N = 29) lesions. Neuroanatomical damage was scored using a semi-quantitative MRI scale. UL function was assessed at body function and activity level. Results CDGM lesions were more pronounced compared to PWM lesions (p = 0.0003). Neuroanatomical scores were correlated with a higher degree to UL function in the CDGM group (r s = −0.39 to r s = −0.84) compared to the PWM group (r rb = −0.42 to r s = −0.61). Regression analysis found lesion location and extent to explain 75% and 65% (p < 0.02) respectively, of the variance in AHA performance in the CDGM group, but only 24% and 12% (p < 0.03) in the PWM group. Conclusions In the CDGM group, lesion location and extent seems to impact more on UL function compared to the PWM group. In children with PWM lesions, other factors like corticospinal tract (re)organization and structural connectivity may play an additional role.