Nephrosialidosis is a rare subgroup of sialidosis characterized by a progressive and fatal course of nephropathy. The authors report a 2-year-old boy who had suffered from steroid-resistant nephrotic syndrome. Renal biopsy showed diffuse and severe vacuolization of glomerular and tubular epithelial cells. The vacuoles were ultrastructurally membrane bound, most of which were not empty but contained electron-dense material lining the inner surface of the membrane. The pathologic changes were consistent with neuraminidase-deficient disorders, which was later confirmed by biochemical analysis. Although rare, nephrosialidosis should be considered in children with steroid-resistant nephrotic syndrome if renal biopsies exhibit severe vacuolar degeneration of renal epithelial cells.