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Abstract Paleopathological diagnoses provide key information on the macroevolutionary origin of disease as well as behavioral and physiological inferences that are inaccessible via direct observation of extinct organisms. Here we describe the external gross morphology and internal architecture of a pathologic right second metatarsal (MMNS VP‐6332) of a large‐bodied ornithomimid (~432 kg) from the Santonian (Upper Cretaceous) Eutaw Formation in Mississippi, using a combination of X‐ray computed microtomography (microCT) and petrographic histological analyses. X‐ray microCT imaging and histopathologic features are consistent with multiple complete, oblique to comminuted, minimally displaced mid‐diaphyseal cortical fractures that produce a “butterfly” fragment fracture pattern, and secondary osteomyelitis with a bone fistula formation. We interpret this as evidence of blunt force trauma to the foot that could have resulted from intra‐ or interspecific competition or predator–prey interaction, and probably impaired the function of the metatarsal as a weight‐bearing element until the animal's death. Of particular interest is the apparent decoupling of endosteal and periosteal pathological bone deposition in MMNS VP‐6332, which produces transverse sections exhibiting homogenously thick endosteal pathological bone in the absence of localized periosteal reactive bone. These distribution and depositional patterns are used as criteria for ruling out a pathological origin in favor of a reproductive one for unusual endosteal bone in fossil specimens. On the basis of MMNS VP‐6332, we suggest caution in their use to substantiate a medullary bone identification in extinct archosaurians.