Background: Typically, appendicitis is a result of luminal occlusion that leads to ischaemia and eventually to perforation with resultant localised or diffuse peritonitis. Unusual causes have been documented including viral infections, parasites, tuberculosis and neoplasms. These conditions are important to recognise, as they may need additional specific management. Objective: This study aimed to identify the incidence and type of unusual (uncommon) histopathology of appendicitis at three tertiary academic hospitals in the urban population of Johannesburg, South Africa. Methods: A retrospective review was undertaken of histopathological reports of appendix specimens obtained during appendectomies between January 2012 and December 2014, in the three academic hospitals of Johannesburg. Results: A total of 2408 histopathology results were obtained from the National Health Laboratory Services (NHLS), of which 164 specimens were excluded from the study because they were part of colonic resection for unrelated conditions. Of the 2244 specimens included, a normal histopathology was found in 8.8%, 52.7% had acute appendicitis, 30.1% had complicated appendicitis, 3% reported serositis and the unusual pathology was found in 5.3% (119/2244). Among the unusual pathologies, the most common histopathological result was parasites (37%) which was predominated by schistosomiasis (24.3%), followed by neoplasm (20%) and fibrous obliteration (14.2%). Conclusion: Unusual histopathologies represented 5.3% of the appendix specimens in this study with parasites and neoplasms as the leading aetiologies. All appendectomy specimens must be submitted to the pathologist for histological diagnosis, and the result is checked before the patient is discharged or for a more pragmatic recommendation in a public hospital setting, to ensure that the histology result is discussed when the patient returns to the outpatient setting for post-operative follow-up.