Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. A neuropathological grading system was developed to assess the severity of striatal involvement in HD. Postmortem brain specimens from 163 clinically diagnosed HD cases were examined, revealing marked variation in neuropathological severity. A five-grade system (0–4) was established based on macroscopic and microscopic criteria, with grade 0 indicating no abnormalities and grade 4 representing severe involvement. The grade correlates closely with clinical disability. In grade 0, no neuropathological abnormalities were found, suggesting anatomical changes lag behind clinical manifestations. Grade 1 showed microscopically detectable changes, primarily in the medial paraventricular portions of the caudate nucleus (CN), tail of the CN, and dorsal putamen. Neuronal loss increased with grade, with 50% loss in grade 1 and 95% in grade 4. Astrocytic changes were also observed, with significant increases in grades 2–4. The CN showed more severe involvement than the putamen. The study highlights the importance of systematic neuropathological evaluation in understanding HD progression and its relationship with clinical features. The grading system aids in interpreting neurochemical and cytological data, and in understanding clinicopathological relationships. The study also emphasizes the need for careful clinical evaluation in cases without neuropathological evidence of HD. The findings suggest that neuropathological severity in HD can be systematically graded, with implications for future research and clinical studies.Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. A neuropathological grading system was developed to assess the severity of striatal involvement in HD. Postmortem brain specimens from 163 clinically diagnosed HD cases were examined, revealing marked variation in neuropathological severity. A five-grade system (0–4) was established based on macroscopic and microscopic criteria, with grade 0 indicating no abnormalities and grade 4 representing severe involvement. The grade correlates closely with clinical disability. In grade 0, no neuropathological abnormalities were found, suggesting anatomical changes lag behind clinical manifestations. Grade 1 showed microscopically detectable changes, primarily in the medial paraventricular portions of the caudate nucleus (CN), tail of the CN, and dorsal putamen. Neuronal loss increased with grade, with 50% loss in grade 1 and 95% in grade 4. Astrocytic changes were also observed, with significant increases in grades 2–4. The CN showed more severe involvement than the putamen. The study highlights the importance of systematic neuropathological evaluation in understanding HD progression and its relationship with clinical features. The grading system aids in interpreting neurochemical and cytological data, and in understanding clinicopathological relationships. The study also emphasizes the need for careful clinical evaluation in cases without neuropathological evidence of HD. The findings suggest that neuropathological severity in HD can be systematically graded, with implications for future research and clinical studies.