This disclosure provides compositions and methods for the isolation of cells that express c-MET, and in particular circulating tumor cells that express c-MET. The methods can include contacting a biological sample including a c-MET circulating tumor cell with an unbound complex including a capture binding species linked to a solid phase for a time sufficient to allow the unbound complex to bind an extracellular binding domain of the c-MET protein to form a bound complex, and subsequently isolating the bound complex. Compositions, systems, and kits adapted for use with these methods are also provided.