12-port differential S-parameters contain the complete behavior of up to three independent differential channels in a high-speed serial interconnect. Though there are 78 unique elements, when including magnitude and phase information, single-ended and differential forms, and the frequency and time domain descriptions, there are more than 400 different elements. This application note puts into perspective the most important terms and the valuable information that can be extracted about the interconnect performance of these measurements. In particular, we will show how the information about coupling regions can be mined from 12-port measurements.