A novel method is presented for the determination of the thermodynamic behavior and classification of quaternary mixtures. Since the quaternary mixtures are formed by four ternary sub-mixtures, the systematic investigation takes place first in two-dimensional and then in three-dimensional tetrahedrons, presenting the residue curve map with a binodal plot. The mixtures can be classified into four groups, and six rules can be concluded for the change in the type of the nodes and saddles, if a new compound appears. The rules help understand the thermodynamic behavior and complete the engineering design of alternatives. The procedure is demonstrated experimentally on the separation problem of a quaternary mixture based on extractive heteroazeotropic distillation (EHAD).