Pantomime of tool use is a highly sensitive test to detect apraxia. The relationship to real-life performance is however unclear since apraxic patients frequently improve substantially when allowed to actually use tools. In the present study, the neural correlates of pantomimed and actual tool use were directly compared in healthy subjects using an event-related functional magnetic resonance imaging (fMRI) paradigm. Subjects were requested to demonstrate the use of various tools either as pantomimes or with the tool in hand. Movement and pre-movement events were evaluated. The comparison of all conditions versus rest revealed a widespread activation including parietal, posterior temporal, frontal, and subcortical areas with some characteristic activation for the different events. The direct comparison between pantomime and actual use conditions revealed no or only minor differential activations for pre-movement events. During the movement event, actual tool use induced the expected additional activation in sensory and motor areas, but also representations presumably related to tool-use knowledge at parietal, posterior temporal, and frontal sites. The opposite contrast of pantomimed versus actual tool use revealed differential activation only in the left intraparietal sulcus in a corresponding region-of-interest analysis. We conclude that planning and preparing of either pantomimed or actual tool use share large parts of a common network. Characteristic differences in the kinematics and dynamics of both movement conditions may be defined just before or during the initiation of the movement when sensory cues about the tool and environment are available in the actual use condition. Sensory and cognitive cues may provide apraxic patients the capacity to evoke a correct action program despite impaired pantomime.