The design and synthesis of distillation cascades using side-stream columns with less than N - 1 columns (two or one) for separations of relatively ideal four-component mixtures are studied. Condenser and reboiler heat duties are used to compare operating costs of cascades with less than N - 1 columns to base cases with three columns. A dimensionless volume index, Sigma(VjVj/ F-T), is used to compare capital costs. Quaternary feeds containing four of the five components n-butane, n-pentane, n-hexane, n-heptane, and n-octane were simulated using the commercially available software package Aspen Plus version 11.1. Columns were operated at L/D = 1.15(L/ D)(min) and with optimum feed and product withdrawal locations. For systems with low concentrations of one component in the feed, side-stream cascades often show significantly lower operating and capital costs compared to the base cases. Low purity requirements (sloppy separations) also favor side-stream cascades. Tentative heuristics are developed to predict which cascade will have the lowest energy consumption and capital cost.