Tuberous sclerosis complex is associated with radiologically visible abnormalities of brain structure, principally tubers and subependymal nodules. We reviewed the literature on neuroimaging of tubers and subependymal nodules and found qualitative evidence of bilateral, predominantly frontal distribution of tubers and bilateral, predominantly subcortical distribution of subependymal nodules in prior studies of pediatric samples. We studied 25 high-functioning adults with tuberous sclerosis complex and normal IQ, acquiring both dual spin-echo and fluid-attenuated inversion recovery magnetic resonance imaging sequences to optimize radiologic diagnosis of tubers and nodules. Individual lesion maps were then coregistered in a standard stereotactic space to facilitate construction of lesion density maps and estimation of lesion density in cortical and subcortical regions reliably defined by a parcellated template image. We found the highest frequency of tubers in frontal lobes and the highest density of tubers in parietal regions. There was significant regional variation in tuber density but no significant lateralization of frequently bilateral tubers. Nodules were located predominantly in the caudate nucleus and were not significantly lateralized. Tuber and nodule volumes were significantly positively correlated. Tuber volume was larger, on average, in patients with a lifetime history of epilepsy, but there was no correlation between IQ and these measures of lesion load. Contemporary image processing tools can be used to enhance quantitative, whole brain analysis of lesion load in patients with tuberous sclerosis complex.