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We report a case of a 68-year-old man who developed an advanced Triple-Negative Breast Cancer (TNBC) presented as a Carcinoma of Unknown Primary (CUP) at diagnoses. After progressing to first line therapy, the molecular platform EPICUP® was performed and the results suggested breast cancer as origin, although non breast primary tumor was found by imaging techniques; and the patient was treated according to this origin. During the evolution of the disease a nodule appeared in the left breast, and a biopsy confirmed the diagnosis of an infiltrating ductal carcinoma. Male breast cancer (MBC) represents an infrequent and heterogeneous disease, but TNBC in men represents less than 0.02% of total breast cancer cases. Unfortunately, there is no standard of care for MBC, and due to the development of new treatment strategies are focused on women BC, there are less opportunities to participate in clinical trials for MBC. Through the review of a clinical case, we show how the molecular platform could help in finding the origin of the CUP. Moreover, further coordinated multicenter international collaboration is necessary to conduct larger and successful therapeutic clinical trials in MBC, and specifically, male TNBC trials to better understand this rare entity and guide future management strategies.