Recent evidence suggests that there are two possible systems for empathy: a basic emotional contagion system and a more advanced cognitive perspective-taking system. However, it is not clear whether these two systems are part of a single interacting empathy system or whether they are independent. Additionally, the neuroanatomical bases of these systems are largely unknown. In this study, we tested the hypothesis that emotional empathic abilities (involving the mirror neuron system) are distinct from those related to cognitive empathy and that the two depend on separate anatomical substrates. Subjects with lesions in the ventromedial prefrontal (VM) or inferior frontal gyrus (IFG) cortices and two control groups were assessed with measures of empathy that incorporate both cognitive and affective dimensions. The findings reveal a remarkable behavioural and anatomic double dissociation between deficits in cognitive empathy (VM) and emotional empathy (IFG). Furthermore, precise anatomical mapping of lesions revealed Brodmann area 44 to be critical for emotional empathy while areas 11 and 10 were found necessary for cognitive empathy. These findings are consistent with these cortices being different in terms of synaptic hierarchy and phylogenetic age. The pattern of empathy deficits among patients with VM and IFG lesions represents a first direct evidence of a double dissociation between emotional and cognitive empathy using the lesion method.