OBJECTIVE: To test the accuracy of EEG source imaging in epilepsy patients with large cerebral lesions. It is hypothesized that lesions are most likely to change conductivity properties and to significantly impair the accuracy of electromagnetic source imaging (ESI) based on the EEG. This has, however, not been tested in patients' EEG. METHODS: Fourteen patients with focal epilepsy and large cerebral lesions underwent high-resolution (128-256 channels) interictal EEG recordings. Thirteen patients were operated, leading to seizure freedom in 12. The spike sources were localized with a distributed linear inverse solution (LAURA) and compared to the post-operative MRI or the results of other invasive or non-invasive exams. RESULTS: In 12 patients ESI indicated the maximum source of the epileptic activity to be located within the epileptogenic zone (85%). One of the remaining cases was not seizure free after surgery. According to the ESI result, however, the focus was incompletely removed. CONCLUSION: High resolution ESI constrained to the individual anatomy identifies the epileptogenic focus in patients with volume relevant brain lesions with excellent accuracy, comparable to that of other non-invasive methods. SIGNIFICANCE: Our results are of particular clinical importance, as they show that ESI can be extended to patients with large inhomogeneous lesions.