Metastases in skin are malignant neoplasms mainly of epithelial, melanocytic, or mesenchymal origin that involve the areas of the skin overlying the primary lesion.  When the lesions are discovered at the same time as the primary tumors, they are considered Cutaneous metastases are poor prognostic indicators if the lesions are discovered at the same time as the primary tumors. ¹ However, involvement of the skin by systemic hematolymphoid lesions is not considered metastasis. The microscopic appearance and genetic profile are those to the primary tumor. Molecular profile of the metastatic tumor and comparison with any primary tumor (if available) is desirable. Molecular analysis (if available) is desirable to try to detect a genetic signature compatible with primary tumor, even if the primary origin is unknown. ²

 Cancer of unknown primary (CUP) is referring to a malignancy with histologically confirmed metastatic spread while the primary tumor remains elusive . Next-generation sequencing (NGS) has been used to inform a molecular guided treatment strategy to improve outcomes over standard chemotherapy in patients with newly diagnosed CUP. ^3-6