BackgroundChoosing the appropriate treatment approach for a multifocal comminuted open fracture of humerus with severe soft tissue defect is a challenging issue, which could be interesting for every orthopedic surgeon especially for those working in the trauma centers.Case presentationThis study described an innovative approach using titanium elastic nailing to treat a multifocal comminuted open fracture of humerus with severe soft tissue defect. In this study, we report a 40-year-old Persian female patient in whom the treatment achieved complete fracture union and skin graft healing by elastic medullary nailing, vacuum dressing, and skin grafting.ConclusionsElastic medullary nailing is a viable option for reconstruction of simultaneous comminuted fracture and soft tissue defect.