Objectives: Malignant bone tumors and fibro-osseous bone lesions of the skull base are uncommon, although fibrous dysplasia in this anatomic location is not a rare condition. In general, fibro-osseous lesions of the skull are often difficult to classify on either clinical presentation, radiological findings, or histological presentation alone. The objective of this article is to present a probably important differential in the management of bony neoformations of the skull and to highlight the diagnostic difficulties when dealing with osseous and fibro-osseous conditions affecting the craniofacial bones. Design: We present here a novel case of posttraumatic reactive fibrous bone neoformation of the anterior skull base mimicking osteosarcoma in a 16-year-old boy. Results: Diagnostic steps, clinical, histological, and radiological presentation, as well as surgical treatment are described in detail. The international medical literature concerning reactive fibrous bone neoformations is reviewed, and the problem of adjusting the correct differential diagnosis when dealing with fibro-osseous bone lesions of the skull base is discussed. Conclusions: The highlights of this case are an uncommon location of a rare pathological entity, which might constitute an important differential of fibro-osseous conditions affecting the craniofacial bones.