Parosteal osteosarcoma (OS) of the jaw is a rare type of OS with peculiar clinical radiographic and microscopic features. The aim of this article was to report and discuss a case of high-grade parosteal OS in the mandible of a 35-year-old woman. The patient reported sensing mild pain and swelling in the retro molar area on the left side of the mouth for a period of 4 years, despite continuous dental treatment. The radiographic evaluation showed a mixed radiopaque/radiolucent lesion in the body of the left side of the mandible. Destruction of the mandibular cortex in that area was also observed. After the initial histological study, the patient underwent partial hemi-mandibulectomy. Microscopic findings showed a tumor exhibiting spindle cells with nuclear hyperchromasia, moderate pleomorphism, and irregular osteoid formation, with chondroid differentiation noted with tumor-free margins. The immunohistochemical analysis showed the expression of negativity to p53, human epidermal growth factor receptor 2/neu, and positivity to S-100. The diagnosis was high-grade parosteal OS of the jaw. The 4 years clinical and imaging postoperative follow-up showed no evidence of recurrence. The literature on this unusual pathologic entity reviewed and diagnostic challenges described.