Leuprorelin acetate-induced granulomas in subcutaneous injection sites have been occasionally reported, but there have been no detailed morphological examinations. Histopathology of leuprorelin acetate-induced granulomas in six patients was studied, and one of them was evaluated by electron microscopy. Study using haematoxylin and eosin staining revealed that there were many intracytoplasmic vacuoles in the granulomas and degeneration of fat tissue. Ultrastructurally, electron-lucent spherical bodies (microcapsules of leuprorelin acetate products) were observed in the granuloma cells. Needle-shaped crystalloid structures in lipid droplets (degenerated lipid droplets) were observed in the granuloma cells and fat tissue. Degeneration of fat tissues caused by leuprorelin acetate is one of main factors responsible for granuloma formation.