The immunohistochemical profile of a CK7−/CK20+ CUPs should include endocrine markers (Chromogranin, Synaptophysin and CD56) as this profile is unique to Merkel cell carcinomas and small cell carcinomas of the salivary glands, both with perinuclear “dot-like” CK20 staining. Here, SYP is linked to Merkel cell skin cancer.