Open AccessCarcinoma of unknown primary origin (CUP) accounts for 2-10% of all malignancies. The apparent absence of the primary tumour, the development of early, uncommon systemic metastases and the resistance to therapy and poor prognosis are hallmarks of this heterogeneous clinical entity and are a challenge for physicians. The diagnostic workup of patients with CUP includes a large amount of histopathological examination, as well as the use of imaging techniques that often fail to identify the primary tumour. Therefore, the optimal workup and treatment for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for "lost" CUP origin and guide the further treatment approach. We report the case of a 66-year-old man, with mediastinal lymph nodes metastasis of carcinoma and neurological syndrome with diplopia and balance disorders, in which many exams have been performed without finding the primary tumour.