Lipoma is a benign tumor that often arises in the craniomaxillofacial region. Osteolipoma containing bone tissue is very rare and the developmental mechanism is unclear. Mesenchymal stem cells in adipose tissue that have potential to differentiate into fat, bone, cartilage, and vascular components may be involved in the development of osteolipoma, in which adipose and bone tissues coexist. We encountered a patient with osteolipoma that arose in the glabella. We describe the case and the results of an investigation of the presence in lipomas of mesenchymal stem cells with differentiation potential similar to that of normal adipose cells. The patient was a 66-year-old woman. Histopathologically, bone tissue surrounded by fibrous connective tissue was present in the nodular adipose tissue and was diagnosed as osteolipoma. Mesenchymal stem cells were collected by collagenase treatment of lipoma tissue, and their potential to differentiate into fat, bone, and cartilage was shown. On the basis of this study, we suggest that lipoma-derived mesenchymal stem cells are the basis of the pathogenesis of osteolipoma. The conditions that induce differentiation of mesenchymal stem cells into bone remain to be investigated.