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Introduction. The identification of the type and site of origin in undifferentiated tumours of unknown primary site using immunohistochemistry is a frequent requirement in pathology practice. There are many histologic lesions that display similar morphologic aspects, with misdiagnosis potentially resulting in overor undertreatment. This makes the diagnostic accuracy extremely important in the era of targeted therapies. The objective of the study was to evaluate the process of diagnosis in 50 melanoma cases presenting as poorly differentiated or undifferentiated tumours with unknown primary origin, with emphasis on the immunohistochemical algorithm. Methods. 50 cases were selected to analyse the utility of IHC testing in diagnosing poorly differentiated malignancies. The immunohistochemical evaluation was based on the staining percentage of cells: focal positive< 50%, diffuse positive> 50%, negative (-) 0%.