We propose a thermodynamically consistent truncated composition expansion, around the infinite dilute quaternary reference system, to describe the thermodynamic behavior of dilute mixed solutes dissolved in mixed-solvents. The development involves the thermodynamically necessary second-order composition expansion of the species partial molar quantities, whose expansion coefficients encompass true molecular meaning based on their underlying links with the solvation properties of the corresponding infinite dilute reference system. Thus, we provide a rigorous molecular-based interpretation of the expansion coefficients in terms of precisely defined microscopic quantities that describe the mixed solvent environment around all species in solution. Consequently, the proposed second-order truncated composition perturbation expansion applies to any type of quaternary system regardless of its aggregation state, in particular, it converges to the rigorous expressions for quaternary mixtures of imperfect gases obeying the truncated virial equation z = 1 + BP/kT, and it reduces naturally to its second-order truncated ternary and binary counterparts through the identification, and consequent manipulation, of the molecular asymmetries among species giving rise to the system nonidealities. Finally, we highlight the origin and key implications of the thermodynamic inconsistencies encountered in currently used first-order truncated expansions. (C) 2017 Elsevier B.V. All rights reserved.