For a suspected diagnosis of acute appendicitis, appendectomy is one of the most common emergency abdominal operations performed. However, the need for routine histopathological examination (HPE) of all appendectomy specimens has recently been questioned. The aim of this study was to assess whether a routine HPE of appendectomy specimens is needed and whether routine HPE has an impact on further management of patients. From January 2009 to June 2017, all histopathology reports of 4012 consecutive appendectomy specimens for a clinical suspicion of acute appendicitis were retrospectively analyzed in two university hospitals. Out of the 4012 cases, 3530 (88%) patients showed findings consistent with acute appendicitis on HPE. Perforation rate was 5.8% and was significantly higher in male patients (p <0.001) and higher in the > 30 years age group (p= 0.024). Negative appendectomy rate was 5.6% and was significantly higher in female patients (p <0.001). There were 256 (6.4%) patients who demonstrated unusual findings in their HPE, which included chronic appendicitis (n= 207; 5.2%) patients, Enterobius vermicularis (n= 14), Schistosoma (n= 8), Crohn's disease (n= 1), neuroma (n= 10), carcinoid tumour (n= 5) and mucinous cystadenoma (n= 5), mucocele (n= 4) and mucinous cystadenocarcinoma (n= 2). HPE of the appendix does not only confirm the diagnosis of acute appendicitis, but also detects other unusual diagnoses that may have an impact on a patient's management. A number of patients with unusual histopathological findings require anti-helmentic treatment, colectomy, gastroenterology follow-up or periodic surveillance. Hence, all appendectomy specimens must be submitted for routine HPE.