Human subjects can tactually estimate the magnitude of surface roughness. Although many psychophysical and neurophysiological experiments have elucidated the peripheral neural mechanisms that underlie tactile roughness estimation, the associated cortical mechanisms are not well understood. To identify the brain regions responsible for the tactile estimation of surface roughness, we used functional magnetic resonance imaging (fMRI). We utilized a combination of categorical (subtraction) and parametric factorial approaches wherein roughness was varied during both the task and its control. Fourteen human subjects performed a tactile roughness-estimation task and received the identical tactile stimulation without estimation (no-estimation task). The bilateral parietal operculum (PO), insula and right lateral prefrontal cortex showed roughness-related activation. The bilateral PO and insula showed activation during the no-estimation task, and hence might represent the sensory-based processing during roughness estimation. By contrast, the right prefrontal cortex is more related to the cognitive processing, as there was activation during the estimation task compared with the no-estimation task, but little activation was observed during the no-estimation task in comparison with rest. The lateral prefrontal area might play an important cognitive role in tactile estimation of surface roughness, whereas the PO and insula might be involved in the sensory processing that is important for estimating surface roughness.