The frequency of histopathological sampling at autopsy varies, even though inadequate sampling may limit the value of autopsy reports. This study aims to investigate the contribution of histopathology at autopsy in a major teaching hospital. A total of 532 coronial autopsy reports from Manchester Royal Infirmary were analysed retrospectively. Gross and microscopic diagnoses were compared and classified as concordant, discordant, histology needed (i.e. indeterminate or unremarkable gross findings) or autolysed. Revisions made to the cause of death following histopathology were categorised as: altered direct cause of death, altered indirect cause of death, concordant with supportive information, irrelevant or inconclusive. The study was limited to brain, heart, kidney, liver, lung and spleen. Histopathology had been requested in 141 cases (27%), which were further analysed. The greatest discordance between gross and microscopic findings was observed in the lung (11.6%). The organs most frequently requiring histopathology to provide a diagnosis were the kidney and lung, at 52.8 and 28.2%, respectively. Alterations were made to the direct cause of death in 45% of cases where histopathology was taken; it provided additional or supportive information in a further 38%. Diagnoses of primary malignancy had a sensitivity of 74% [confidence interval (CI)=0.59-0.86] and bronchopneumonia had a sensitivity of 45% (CI=0.29-0.62). Histopathology has a major impact on the interpretation of organ pathology and determining a cause of death at autopsy.