Vanishing bone disease is a rare idiopathic disease, leading to extensive loss of bony matrix, replaced by proliferating thin-walled vascular channels and fibrous tissue. There are >191 cases reported in the English literature. Gorham and Stout made the first overview of the disease in 1955 and they first presented 24 cases known at that time. The etiology remains speculative, the prognosis unpredictable, and effective therapy still unknown. The disease can be monostotic or polyostotic although multicentric involvement is exceptional. We report 2 cases of a histologically studied vanishing bone disease involving the humerus and the femoral head. The patients' past history was noncontributory. The radiographic study revealed a destructive lesion of the left humerus in the first case, and complete disappearance of the femoral head in the second case. Laboratory findings including hormonological tests revealed no evidence of metabolic, immunologic, neoplastic, or infection etiology. Histopathological findings of the 2 cases revealed thickened bone of lamellar structure without marrow cavities next to fibrous tissue, with few fibroblasts and a small number of newly formed vascular channels. The prognosis varies from slight disability to death by involvement of vital skeletal structures. The treatment of vanishing bone disease is controversial. Several treatment modalities have been proposed. Surgical intervention has been suggested as a method of choice by many authors and concerns local resection of the affected bone, with or without replacement prosthesis or bone grafts.