Background: Metastatic tumours sometimes present with neuropsychiatric symptoms, however psychiatric symptoms as rarely the first clinical manifestation. Cutaneous melanoma is the third most common cause of brain metastasis, with known risk factors increasing the chance of such central nervous system metastization. Objectives: We present a clinical report of delirium as the first clinical manifestation of melanoma brain metastases, illustrating the relevance of an adequate and early differential diagnosis. Methods: In addition to describing the clinical case, searches were undertaken in PubMed and other databases using keywords such as “brain metastasis”, “melanoma”, “agitation”, “psychiatric” and “delirium”. Results: We here report the case of a 52-year-old female patient evaluated by Liaison Psychiatry after sudden onset of delirium while admitted at the Gastroenterology Department to study a hypothesis of pancreatitis. A head CT scan identified brain metastases, and after further examination, including brain biopsy, melanoma brain metastization was confirmed. Discussion: Some of the diagnostic challenges of psychiatric symptoms associated with secondary brain tumours are discussed, underlining the importance of an adequate differential diagnosis when working in Psychiatry Liaison.