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Fat embolism syndrome (FES) can be challenging to diagnose by forensic pathologists. For the diagnosis of FES, there is no benchmark test. Postmortem diagnosis requires a full autopsy and specific ancillary examination. However, the high variability in the clinical presentation of FES represents a relevant issue, and there is no consensus on the postmortem assessment. This is the case of a 33-year-old man who died of FES one week after a car accident. He suffered multiple fractures, but was hemodynamically stable and showed no neurological changes. The patient died a few days after hospital discharge. Additionally, he had osteogenesis imperfecta type III, a genetic disorder associated with bone fragility. To the best of our knowledge, no study has assessed whether and how osteogenesis imperfecta contributes to the onset of FES. Despite the heterogeneous manifestations of FES, the present case met many of the proposed clinical and histological diagnostic criteria. Therefore, we briefly review FES diagnostic criteria, show the postmortem diagnostic workup, and discuss the hypothetical link between osteogenesis imperfecta and FES. [ABSTRACT FROM AUTHOR]