Rationale:Osteosarcoma, a malignant bone tumor, rarely occurs in the sternum, especially the fibroblastic type, and is associated with poor survival. This case report describes a patient with a neoplasm of the sternum who underwent tumor resection 3 times and reconstruction twice because of the high risk of recurrence.Patient Concerns:A 60-year-old Chinese man presented with a 3-cm palpable bulging mass located in front of his sternum. Chest computed tomography (CT) revealed an anterior chest wall neoplasm with sternal destruction.Diagnosis:Pathological examination revealed that the mass was a low-grade malignant primary fibroblastic osteosarcoma.Interventions:Locking plates were used for chest wall reconstruction, demonstrating good structural stability and economic applicability. Regarding the ineffectiveness of current therapies, whole-exome sequencing was conducted, and no targets matched any of the currently available agents.Outcomes:No recurrence was found on regular reexamination.Lessons:Surgery is the first choice of treatment for patients with primary fibroblastic osteosarcoma of the sternum. The reconstruction-locking plate is a good alternative for chest wall reconstruction. Whole-exome sequencing can shed new light on this uncommon disease and help identify novel therapeutic targets.