Although hyperacute rejection has been clinically and pathologically fully described in recipients of other solid organ transplants, to our knowledge, there have been no previous fully documented cases in recipients of lung transplants. This case of clinical hyperacute rejection is corroborated by a positive, donor-antigen-specific IgG-mediated lymphocytotoxic crossmatch (LXM), and demonstrated histopathologic, immunofluorescent, and electron microscopic features consistent with hyperacute rejection as described in other organs. Features of diffuse alveolar damage, neutrophilic infiltrates, and endothelial and epithelial damage with IgG-fluorescent staining within alveolar spaces and septae were demonstrated. The management of hyperacute rejection and its outcome are reviewed. Historically a pretransplant crossmatch is not considered a routine part of lung transplantation. The outcome of this patient suggests that LXM should be performed routinely prior to lung transplant in all patients with high panel-reactive antibodies, and should be performed whenever circumstances permit.