Hypercalcemic nephropathy has been classified as a tubulointerstitial renal disease. The presence of glomerular pathologic findings attributable to hypercalcemia has been observed in only a few patients and therefore has been considered an unusual finding. In the current study, calcium deposition within glomeruli was investigated in 2 patients with extreme elevations in serum calcium levels and hypercalcemic nephropathy. The study material consisted of a renal biopsy specimen from a 31-year-old woman (patient 1) who had T-cell lymphoma/leukemia and a serum calcium level of 20.2 mg/dL (5.0 mmol/L) and autopsy kidney specimens from a 19-year-old woman (patient 2) who was being evaluated for primary hyperparathyroidism and a calcium level of 18.4 mg/dL (4.6 mmol/L). The renal biopsy specimen for patient 1 exhibited calcium deposits present in the glomerular capillary basement membranes, where they were associated with segmental sclerosing lesions (21% of glomeruli). Nine percent of the cortical tubules contained calcifications. In patient 2, calcium was found in the mesangial areas in 95% of glomeruli, filling the Bowman space in 7% of glomeruli, or associated with capillary basement membranes and segmental sclerosing lesions (12% of glomeruli). Fifteen percent of cortical tubules, 4% of outer medullary tubules, and 40% of inner medullary tubules were calcified. In neither case was there immunofluorescence or electron microscopic evidence of primary glomerular disease. Thus, glomerular calcification may exceed that occurring in the cortical and outer medullary tubules and may play a significant role in the loss of renal function in hypercalcemic nephropathy. Glomerular calcinosis may also be recognized as an additional cause of segmental glomerulosclerosis and nephrotic range proteinuria in patients with extremely high levels of serum calcium.