An autopsy case of Sandhoff disease in a 2‐year‐old boy is reported. Diagnosis was established by enzyme assay, which demonstrated total deficiency of hexosaminidase in the serum. Histochemical examination, using hematoxylin‐eosin (H & E) and Luxol fast blue (LFB) stain, showed accumulation of LFB‐positive material not only in cells of the cerebrum, cerebellum, spinal cord, and peripheral nervous system, but also in reticuloendothelial cells of the lymph nodes, spleen, thymus, and liver, in podocytes of renal glomeruli, in all types of renal tubular cells, in endothelial cells of small vessels, in fibroblasts, and in epithelial cells of the epididymis and ductus deferens. Electron microscopic examination showed that these deposits contained electrondense membranous bodies. Lipid analysis demonstrated a marked elevation of ganglioside G_M2 and its asialo derivative in the brain and liver. Accumulation of globoside was found in the liver, kidney, and spleen. There was complete absence of hexosaminidase in the brain and liver.