The MHC class I chain-related (MIC) proteins are related to the Major histocompatibility complex (MHC) class I proteins which are ubiquitously expressed and mediate the recognition of intracellular antigens by cytotoxic T cells. The MHC class I chain-related (MIC) proteins are recognized by NKG2D, a receptor on NK and T cells, and promote anti-tumor activity. MICA, a member of the MIC family, is widely expressed on many tumors, and it is the MICA/NKG2D interaction that is thought to stimulate the anti-tumor reactivity by T lymphocytes. MICA is present in virtually every tissue except the nervous system, suggesting that MIC protein expression may only be one component of the anti-tumor activity of the immune system.