This paper discusses the theoretical and experimental aspects of modeling of irregular mixed-layer structures of chemically nonhomogeneous single crystals based on X-ray diffraction data. The available data on natural and synthetic single crystals of different structural types belonging to different polysomatic and isomorphic series are reviewed. Two basic types of structure are described, and criteria for their diagnostics by diffraction patterns are formulated. The range of substances to which this approach is applicable is analyzed. It is shown on particular examples that the statistical probability-based model of an irregular mixed-layer structure is applicable to quantitative description of lamellar isomorphism, fine oscillation zoning, decay structures of solid solutions, and nonhomogeneous organic thin film structures.