Brain banks allow researchers access to tissue from well-characterised neurodegenerative disease cases. Fixed tissue employed for diagnosis is often not appropriate for research and frozen tissue is therefore made available. Many brain banks use a protocol where half the brain is fixed and half frozen. Recently a study has shown that there can be asymmetry in protein deposition between the hemispheres especially with tau and TDP-43. We aimed to test this hypothesis by prospectively taking bilateral cortical blocks from 30 brains on arrival, and immunostaining to assess the degree of asymmetry. In 6 out 14 cases of AD (Alzheimer's Disease) (Modified Braak Stage V-VI), there was some asymmetrical staining for tau. In 2 cases, there was moderate discrepancy for tau staining between left and right calcarine cortices. However, careful analysis in both these cases revealed discrepancies in tau staining in adjacent regions even on the same side. The α-synuclein staining showed asymmetry in one case only, the Aβ showed only mild asymmetry in 3 cases of AD. The TDP-43 pathology appeared symmetrical in the 2 cases of frontotemporal lobar degeneration with motor neurone disease, but there was asymmetry noted when seen in conjunction with AD. In conclusion, there is the potential for asymmetrical pathology in neurodegenerative diseases and caution should be maintained when freezing half and fixing half of the brain in neurodegenerative diseases. Nevertheless, marked variability in staining can also be identified in adjacent cortical areas so there is no guarantee that an alternative strategy would be superior.