Diffusion Weighted Imaging (DWI) is effective in identifying microstructural cerebral parenchymal changes. We studied the diffusion characteristics of hamartomas and normal white matter in cases with tuberous sclerosis (TS).Diffusion weighted images of 6 TS cases (ages between 3 - 15 years, mean 9.0 years, SD 4.4 years) that presented to our center for magnetic resonance (MR) imaging have been retrospectively evaluated. In addition to 56 non-calcified hamartomas of TS patients, apparent diffusion coefficient (ADC) values measured from frontal, parietal normal white matter, and basal ganglions of TS patients were compared with values obtained from 9 normal subjects (ages 1 - 13 years, mean 8.9 years, SD 3.4 years). Hamartomas were divided into 3 subgroups based on their locations, and the ADC values measured in these groups were compared.ADC values of all hamartomas were between 838 and 2230, with a mean value of 1408 mm (2)/sec x 10(-3) (SD: 273.2); ADC values of the white matter of normal subjects were between 695 and 857, with a mean value of 776.1 mm (2)/sec x 10(-3) (SD: 44.23) (p < 0.0001). ADC values of subependymal nodules, white matter hamartomas, and subcortical tubers were 838-2230 (mean: 1440.5 mm (2)/sec x 10(-3); SD: 526.46), 1046-1622 (mean: 1328.6 mm (2)/sec x 10(-3); SD: 189.4), and 981-1973 (mean: 1417.4 mm (2)/sec x 10(-3); SD: 219.5), respectively (p = 0.666).Diffusion characteristics of white matter hamartomas resulting from TS clearly differ from those of normal white matter, but no significant difference was observed in ADC values of these lesions based on their locations. Moreover, the ADC measurements of normal white matter in these cases did not differ from those of the control group, indicating that the disease does not cause a common explicit damage in white matter and central gray matter, other than hamartomas, which can be detected by DWI. DWI may only be used in the differential diagnosis of hamartomas from secondary lesions with T1 and T2W signal intensities similar to those of hamartomas and with different diffusion characteristics.