In this paper, we aim at providing results concerning the application of desktop systems for rapid prototyping of medical replicas that involve complex shapes, as, for example, folds of a colon. Medical replicas may assist preoperative planning or tutoring in surgery to better understand the interaction among pathology and organs. Major goals of the paper concern with guiding the digital design workflow of the replicas and understanding their final performance, according to the requirements asked by the medics (shape accuracy, capability of seeing both inner and outer details, and support and possible interfacing with other organs). In particular, after the analysis of these requirements, we apply digital design for colon replicas, adopting two desktop systems. The experimental results confirm that the proposed preprocessing strategy is able to conduct to the manufacturing of colon replicas divided in self-supporting segments, minimizing the supports during printing. This allows also to reach an acceptable level of final quality, according to the request of having a 3D presurgery overview of the problems. These replicas are compared through reverse engineering acquisitions made by a structured-light system, to assess the achieved shape and dimensional accuracy. Final results demonstrate that low-cost desktop systems, coupled with proper strategy of preprocessing, may have shape deviation in the range of ±1 mm, good for physical manipulations during medical diagnosis and explanation.