Abstract: Argyrophilic grains are discrete punctate structures that bind to silver stains; they can be observed within the neuropil of the limbic system, particularly in the elderly. It has been reported that argyrophilic grains are more frequent in patients with corticobasal degeneration (CBD) compared with the elderly population in general. To determine the frequency and significance of argyrophilic grains in CBD, we examined the temporal lobes from 35 patients with autopsy-proven CBD (mean age, 69.1 years) and 28 patients with argyrophilic grain disease (mean age, 95.7 years). Grain distributions and densities were evaluated semiquantitatively using Gallyas-Braak stains and immunohistochemistry with AT8 and RD4 antibodies. Argyrophilic grains were observed in all CBD cases (100%) despite a lower average age at death in this population. We also observed the following features that were specific to argyrophilic grains in CBD: 1) grains were likely to be widespread throughout the temporal lobe, 2) grains were consistently found with abundant argyrophilic threads, and 3) the ultrastructure of grains contained paired helical filaments with a periodicity of 120 to 130 nm. In conclusion, we confirm that argyrophilic grains in CBD are specifically related to the 4-repeat tau pathology of CBD and are not simply a result of aging.