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Red flags (signs and symptoms that might raise suspicion of serious spinal pathology) have historically been used by clinicians to identify serious spinal pathology. Currently, there is an absence of high-quality evidence for the diagnostic accuracy of most red flags. This framework is intended to provide a clinical-reasoning pathway to clarify the role of red flags. J Orthop Sports Phys Ther 2020;50(7):350\u2013372. 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