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Unicameral bone cysts (UBCs) are benign tumor-like lesions that commonly occur in the diaphyseal or metaphyseal region of the long bones within the first 2 decades of life. Until today, the pathogenesis of UBC has been unclear, but mechanisms such as vascular occlusion or a response to trauma have been supposed. During the past decade, in particular, the genetic aspects of the development of this rare lesion have been discussed. We present the first case of mirror image monozygotic twins with a mirror image UBC of the calcaneus. Our findings reinforce the importance of additional studies to understand the significance of cytogenetic factors in the etiology of UBC.