Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) is a common complication contributing to death. ACS can present as sudden, unexpected death, and the medical history of SCD may not be immediately available for the medical examiner. Forensic implications for ACS are more likely to be encountered in patients with the HgbSC variant of SCD because the presence of a spleen may obscure recognition of SCD. Pathologists commonly observe small bone marrow emboli within the lung vasculature postmortem after trauma or vigorous cardiopulmonary resuscitation. Consequently, the finding of pulmonary marrow emboli in ACS may be dismissed as incidental and nonpathologic. Pulmonary marrow emboli cause ACS in patients with SCD, when there is parvoviral infection with marrow necrosis. Pulmonary marrow embolism in ACS has special significance in forensic pathology. Forensic pathologists investigate sudden, unexpected deaths during exertion, such as athletics, police pursuit, or military training. A causal relationship linking sickling hemoglobinopathy with physical exertion and sudden death has been reported. In the absence of a specific and timely medical history of SCD, and with a normal or enlarged spleen in patients with HgbSC, pathologists may wrongly dismiss bone marrow emboli as consequences of cardiopulmonary resuscitation, when those emboli might actually have been causative of fatal ACS.