This study presents a neuropathological classification system for Huntington's disease (HD) based on the severity of striatal involvement. The classification, ranging from grade 0 to 4, was established using macroscopic and microscopic criteria and correlates closely with clinical disability. Grade 0 cases showed no discernible neuropathological abnormalities, while grade 4 cases exhibited severe atrophy and neuronal loss in the caudate nucleus (CN) and putamen. The earliest changes were observed in the medial paraventricular portions of the CN and dorsal part of the putamen. Neuronal loss and astrocytic gliosis progressed from grade 1 to 4, with grade 4 cases showing a predominantly astrocytic composition. The study also found that the severity of neuropathological changes in the striatum varied among cases, with grade 1 and 2 cases reflecting early cellular and biochemical changes. The findings highlight the importance of a systematic approach to neuropathological grading in HD, which can aid in interpreting neurochemical and cytological analyses and understanding clinicopathological relationships.This study presents a neuropathological classification system for Huntington's disease (HD) based on the severity of striatal involvement. The classification, ranging from grade 0 to 4, was established using macroscopic and microscopic criteria and correlates closely with clinical disability. Grade 0 cases showed no discernible neuropathological abnormalities, while grade 4 cases exhibited severe atrophy and neuronal loss in the caudate nucleus (CN) and putamen. The earliest changes were observed in the medial paraventricular portions of the CN and dorsal part of the putamen. Neuronal loss and astrocytic gliosis progressed from grade 1 to 4, with grade 4 cases showing a predominantly astrocytic composition. The study also found that the severity of neuropathological changes in the striatum varied among cases, with grade 1 and 2 cases reflecting early cellular and biochemical changes. The findings highlight the importance of a systematic approach to neuropathological grading in HD, which can aid in interpreting neurochemical and cytological analyses and understanding clinicopathological relationships.