Animal experiments have found microstructural changes in the cerebellum in response to long-term motor skill activity that include an increase in the number of synapses per neuron, glial cell volume, and capillary density. The sum of those microstructural changes were reported to lead to regional volume changes. We investigated whether professional keyboard players, who learn specialized motor skills early in life and practice them intensely throughout life, have larger cerebellar volumes than matched non-musicians. Total brain volumes and cerebellar volumes were measured using high-resolution T1-weighted MR images from a large prospectively acquired database of musicians and non-musicians, selecting all right-handed professional keyboard players (n = 56, 28:26 male:female) and age, gender and height matched non-musicians. To correct for intersubject variability, absolute cerebellar volume (aCV) was related to total brain volume (tBV), after demonstration of a strong correlation between these variables (r=0.686, p < 0.001), as the relative cerebellar volume (rCV where rCV = aCV/tBV %). A highly significant effect of gender was found for all variables: males having significantly greater tBV and aCV but females having significantly greater rCV, therefore the male and female groups were analyzed separately. A significant difference in rCV (p<0.025) was found between the musicians (10.38%, SD 0.64) and non-musicians (9.96%, SD 0.71) in the male group. A significant positive correlation (r 2 = 0.545, p = 0.003, two-tailed) was found between intensity of practice (average hours/day of practice over lifetime of training) and rCV in the male musician group. In the female group, there was no significant difference noted in rCV and aCV between musicians and non-musicians, however there was a strong trend in tBV difference (p=0.082) with the female musicians having greater mean tBV than the female non-musicians. Although self-section for musicianship by individuals with innate brain structural differences cannot be completely ruled out, finding an association between rCV and greater intensity of practice in male musicians might indicate structural adaptation to long-term motor activity in the human cerebellum. The absence of an effect of musicianship on cerebellar volume in the female group may be explained by a possible ceiling effect in the female group as it is demonstrated that females in general have relatively larger cerebellar volumes than males. An effect of musicianship may be present in other brain regions in the female group considering the strong trend for a difference in absolute brain volume between the female musicians and non-musicians.