Intraosseous lipoma is a rare bone tumor that may be encountered in clinical practice. It is benign and is described as a well-defined, radiolucent lesion that must be differentiated from other lytic lesions. Most of these lesions may be treated without surgery; however, when surgery is needed, the classic approach involves curettage and packing using autologous bone grafts, allografts, or synthetic bone substitutes. This article reports two cases using a synthetic bone substitute, TheriLok, to fill the void made from surgical curettage of the intraosseous lipoma. Both patients tolerated the TheriLok bone substitute without developing adverse reactions and precluded the need for a secondary donor site.