A 48-year-old female with a complaint of persistent pain referred to the Imam Khomeini (Tehran, Iran) in 2018. Based on the radiographic findings, radiolucent lesion found in the right mandible and she had alendronate administration approximately for 10 years. Since the past 6 months, the lesion detected in the right mandible. According to the computed tomography scan, a large lytic destructive lesion with a soft-tissue component was seen at the right mandibular ramus. Microscopic examinations revealed the proliferation of anaplastic spindle-shaped cells arranged in interlacing bundles and whorled patterns. Nuclear polymorphism, scattered cells with hyperchromatic nuclei and increased mitotic activity were notable. Immunohistochemistry findings for tissue section composed of spindle cell proliferation revealed Ki67 (20% positive in hotspots), scattered positive right side incisional biopsy was done. The observation revealed hyperplastic and disorganized squamous epithelial lesion, suggestive of spindle squamous cell carcinoma and osteonecrosis in this patient.