Labyrinthine sequestrum, a rare form of labyrinthitis, is highly distinct from the more commonly encountered labyrinthitis ossificans based on its unique clinical, radiologic, and histologic characteristics. The study included 4 such patients who had undergone clinical and laboratory investigations, computed tomography (CT), and magnetic resonance imaging (MRI) assessments followed by surgical procedures and pathological evaluation. Their major symptoms were otorrhea, otalgia, tinnitus, and profound hearing loss. Imaging studies showed an osteolytic soft mass with calcified debris in the inner ear, and the bony labyrinth was eroded partly or completely by granulation mass, with loss of bony morphology. Further pathological examination was coincident with inflammatory granulation tissue with some calcification or osseous tissue. The disease process is attributed to chronic osteomyelitis due to the presence of osteonecrosis. Prompt CT and MRI examinations and optimal therapeutic management facilitate definitive diagnosis and protect against fatal complications.