A systematic procedure is presented for the synthesis of chromatography-crystallization hybrid separation processes, which are widely used in the fine chemical and pharmaceutical industries for the recovery of high-purity products. The separation objectives and input information such as chromatograms and solid-liquid equilibrium phase diagrams are first identified. Second, the basic process structure is determined by specifying the order in which chromatography and crystallization units are used in the process. Third, the fractions of the chromatographic effluent and their destinations are specified to complete the process flowsheet. Finally, the generated process alternatives are evaluated to select the best one. Design heuristics are provided to assist decision making. The application of the procedure is illustrated using three examples.