BACKGROUND Successful preoperative diagnosis of a branchial cyst requires a systematic approach. The aim of this study was to evaluate methods of investigation of a lateral neck swelling suspicious for a branchial cyst, and to highlight cases where a less benign cause for the swelling should be suspected and therefore management altered appropriately. METHODS A retrospective case study of 24 patients with presumed branchial cysts managed operatively was undertaken. Demographic, clinical, imaging, cytology and histopathological data were analysed to formulate an approach to the work-up of a lateral neck swelling suspected to be a branchial cyst. RESULTS All 24 patients presented with a lateral neck mass thought to be a branchial cyst preoperatively underwent preoperative fine-needle aspiration cytology. The overall accuracy of cytology in predicting a benign branchial cyst histopathologically was 83.3% (20 out of 24). CONCLUSIONS Successful preoperative diagnosis of a branchial cyst requires a combination of imaging and cytology. If there is concern that a lateral neck swelling is not a branchial cyst on clinical, imaging or cytological features, then a full preoperative work-up, including computed tomography scan of the neck and upper aero-digestive tract endoscopy should be performed, prior to an excisional biopsy.