Chronic right iliac fossa (CRIF) pain in children is associated with repeated hospital attendance, inconclusive investigations, and missed school days. There is increasing evidence for the role of laparoscopic appendectomy for the management of CRIF pain. However, currently there is no substantial evidence to correlate histological changes identified in the appendixes removed with resolution of pain. This study collected prospective data for a single surgeon's series of laparoscopic appendectomy performed for CRIF pain between 2003 and 2014. Forty patients with a median age of 13 years (range 5-19 years) underwent laparoscopic appendectomy for CRIF pain. Twenty-nine patients (73%) had macroscopically normal appendixes, but histological changes were identified in 28 patients (70%). Other findings at laparoscopy included gynecological pathology (ovarian/para-ovarian cysts), unfixed mobile caecum, and a well-defined peritoneal band extending from the caecum to the anterolateral abdominal wall (caeco-peritoneal band). Patients were followed up for a median of 2 months (range 1-15 months). All patients reported resolution of CRIF pain. Laparoscopic appendectomy appears to be an effective treatment for CRIF pain, while also providing the opportunity to diagnose and treat potential sources of CRIF pain other than the appendix. Consistent with the literature, a small number of patients appear to have resolution of pain, despite no histological change being identified in the appendix removed and no other pathology having been identified. The same histological changes commonly seen have also been demonstrated in appendixes removed incidentally. Caution therefore should be applied when interpreting the significance of histological changes seen.