The clinical and pathological findings, including those of immunohistochemical and ultrastructural studies, of two cases of tumoral calcinosis-like lesion (TCL) are described. Both cases were associated with chronic renal failure and hyperparathyroidism. One case presented as a rapidly growing 20-cm multiloculated, cystic, calcific gluteal mass on the sacrum, which was not clinically suspected to be related to hyperparathyroidism. The other case presented as a 2.5-cm calcific mass on the right foot that recurred after surgical excision as a 7-cm mass, which was clinically presumed to be related to secondary hyperparathyroidism. Light microscopic and immunohistochemical studies on both cases and ultrastructural studies on one case indicated that the calcifying process involved histiocytes and osteoclast-like giant cells of histiocytic origin lining the cystic cavities. Hydroxyapatite crystal formation and calcification appeared to develop predominantly from intracytoplasmic membrane bound vesicles and also from mitochondria. These findings are similar to those recently reported for familial tumoral calcinosis, which support its having a mechanism of calcification comparable with that of a TCL.