We report a case of intractable epilepsy caused by tuberous sclerosis with multiple tubers that was treated successfully by single resection of a tuber A 2-year-old boy developed tonic spasm-like seizures at the age of 4 months and the frequency of the seizures increased despite therapy with various anticonvulsants. He had no neurological deficits, and his intelligence was normal. MRI showed lesions in the left frontal and the right parietal lobe, and EEG (electroencephalogram) demonstrated sharp waves and spike-and-wave complex bursts over the right parietal region. Subdural electrodes were implanted over these lesions, and ictal low-voltage fast waves were demonstrated on the right parietal lesion. Therefore the right cortical lesion and the epileptogenic cortex were resected. Multiple subpial transaction was also added in the irritative cortex. Histological examination proved that the lesion was a tuberous sclerosis complex (TSC) tuber. Since surgery, the patient has remained seizure-free for 2 years. In patients with multiple TSC tubers in the cortex, we suggest that seizures can be suppressed by single resection of a tuber if the tuber can be identified as epileptogenic before surgery.