Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

•This ESMO Clinical Practice Guideline provides key recommendations for managing cancer of unknown primary (CUP).•The guideline covers CUP diagnosis, risk assessment, classification, treatment and follow-up.•Differential diagnostic algorithms for discrimination between CUP and other cancers are provided.•The author group includes multidisciplinary experts from different institutions in Europe, Australia and the United States.•Recommendations are based on available scientific data and the authors’ collective expert opinion.•In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach.