Management of lateral cystic neck masses with no apparent upper aerodigestive tract primary tumour in adults is controversial. Imaging modalities and fine needle aspiration cytology often struggle to distinguish the presence of malignancy. This study entailed a multicentre retrospective review of all patients with isolated lateral cystic neck masses from 2012 to 2018 in three Welsh health boards, utilising demographic data and first-line investigations (ultrasound scanning and fine needle aspiration cytology) to develop an evidence-based predictive tool for risk of malignancy. It was found that 29.1 per cent of cystic lesions were malignant on final histology. Age, male gender, non-benign ultrasound scan findings and fine needle aspiration cytology were significant risk factors on univariate analysis. The final multivariate analysis predicted a risk of malignancy ranging from 2.1 to 65.0 per cent depending on the covariate pattern. Smoking status was non-significant. A rigorous, risk-stratified approach to the management of these patients should aid the clinician in minimising morbidity and optimising resources.