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Cytokeratins (CK) are a large family of cytoskeletal filaments, essential for normal structure and function of all mammalian epithelial cells. The CK filaments are obligatory heterodimers each formed tetrameric by two different proteins, one acidic (type I) and one basic-to neutral (type II) CK protein. CK pan is a broad-spectrum cytokeratin that stains both low and high molecular weight cytokeratins. Expression is found in all epithelial cell types that are documented to express cytokeratins. Anti-CK pan staining is observed in the vast majority of epithelial cancers, but can be absent in a fraction of epithelial tumors. For most epithelial tumor types the rate of CK pan negativity is low with 0.5-5% making it a useful tool for differentiating epithelial from non-epithelial tumors.