Problem: If no obvious primary tumour is detectable in metastatic tumours (cancer of unknown primary, CUP), it should nevertheless be identified if possible, as specific therapy achieves better results than empirical, palliative treatment of CUP.

Methodology: The new guideline of the European Society of Medical Oncology (ESMO) defines algorithms for the evaluation of CUP, in which radiological and nuclear imaging procedures play a central role. Important clues to a possible primary tumour are the size and morphology of foci and the presence of a dominant lesion, as well as the pattern of hematogeneous metastatic spread in affected organs, and the anatomical distribution of affected lymph nodes.

Conclusion: In patients with metastases, imaging plays an important role in identifying a possible primary tumour, but the diagnosis must be made with knowledge of the clinical and immunohistochemical results. In difficult cases, there should be interdisciplinary consultation between reference oncology, radiology, and pathology on the presence of CUP.