Melanoma Inhibitory Activity Protein (MIA) is an autocrine growth regulatory protein secreted from chondrocytes and malignant melanoma cells, which was the first discovered member of a family of secreted cytokines termed the MIA/OTOR family. The four known members of this family: MIA, MIA2, OTOR and TANGO each contain a Src homology-3 (SH3)-like domain. MIA acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas, in an autocrine fashion and promotes melanoma metastasis by binding competitively to fibronectin and laminin in a manner that results in melanoma cell detachment from the extracellular matrix in vivo. The protein MIA has been shown to represent a very sensitive and specific serum marker for systemic malignant melanoma that might be useful for staging of primary melanomas, detection of progression from localized to metastatic disease during follow-up, and monitoring therapy of advanced melanomas. Elevated levels of MIA may represent a clinically useful marker for diagnosis of melanoma metastasis as well as a potential marker for rheumatoid arthritis.