Background: The vermiform appendix is a cause of significant morbidity and at times mortality, and a frequent surgical specimen, not only because most surgeons feel it is a vestigial but potentially troublesome organ that should be extirpated even when ‘quiet’. Although acute appendicitis is the most common lesion diagnosed in appendix specimens, it is clear that there is more to appendiceal disease than acute appendicitis. A lot of authors have published studies touching on various aspects of appendiceal disease as seen in Nigeria but there is a dearth of literature on multi-centre studies, carried out with a view to comparing the surgical pathology of the appendix in different geographical zones of the country. The justification for this being that Nigeria represents an amalgamation not only of diverse ethnic nationalities but also of diverse geographical characteristics; all of which have a bearing on the development of appendiceal disease. Method: We retrospectively reviewed all appendectomy specimens received over a 7 year period, between January, 2001 and December, 2007, in 2 teaching hospitals representing the southwest and southeast zones of Nigeria; the Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife (OAUTH) and University of Nigeria Teaching Hospital, Enugu (UNTH). Details of data on patients’ age, sex, diagnosis at presentation and the gross and microscopic characteristics of the specimens were retrieved from the archives of the morbid anatomy departments of the respective institutions. Results: A total of 378 and 82 appendectomy specimens in OAUTH and UNTH respectively were seen in this study. A variety of histological lesions were seen, comprising acute appendicitis, chronic non specific appendicitis, granulomatous appendicitis, eosinophilic appendicitis, follicular hyperplasia, carcinoid tumour, mucinous cystadenoma and inflammatory pseudotumour. Acute appendicitis accounted for majority of cases diagnosed, representing 297 cases or 78.6% in OAUTH, 35 cases or 42.7% in UNTH, and 332 cases or 72.2% overall. The negative appendectomy rate was 6.9% in OAUTH; 41.5% in UNTH and 13% overall. The mean age was 25.7 years in OAUTH and 27.4 years in UNTH; while the peak age frequency was in the 21 – 30 years age group in both cohorts. The male to female ratio was 1.2:1 and 1:1 in OAUTH and UNTH respectively. Conclusion: Acute appendicitis was the most frequently diagnosed lesion of the appendix, with a peak incidence in young adults. There was significant concordance between the gross and microscopic features of acute appendicitis. There was also a preponderance of features associated with severity in a majority of the cases reviewed in both centres, cutting across gender and all age groups. Therefore clinical factors such as late presentation rather than age or gender may be the key determinant of severity in acute appendicitis. One major drawback experienced in this study was the lack of consensus in diagnostic criteria for the determinants of the subsets in acute appendicitis and diagnosis of contentious lesions such as chronic appendicitis and follicular hyperplasia. It is hoped therefore that the findings from this study will give impetus to the development of a minimum data set for the reporting of appendix specimens so that inter and intra observer variations will be minimized.