Cleft lip and palate reconstructive surgery requires thorough knowledge of normal and pathological labial, palatal, and velopharyngeal anatomy. This study compared two software algorithms and their 3D virtual anatomical reconstruction because exact 3D micromorphological reconstruction may improve learning, reveal spatial relationships, and provide data for mathematical modeling. Transverse and frontal serial sections of the midface of 18 fetal specimens (11th to 32nd gestational week) were used for two manual segmentation approaches. The first manual segmentation approach used bitmap images and either Windows-based or Mac-based SURFdriver commercial software that allowed manual contour matching, surface generation with average slice thickness, 3D triangulation, and real-time interactive virtual 3D reconstruction viewing. The second manual segmentation approach used tagged image format and platform-independent prototypical SeViSe software developed by one of the authors (F.W.). Distended or compressed structures were dynamically transformed. Registration was automatic but allowed manual correction, such as individual section thickness, surface generation, and interactive virtual 3D real-time viewing. SURFdriver permitted intuitive segmentation, easy manual offset correction, and the reconstruction showed complex spatial relationships in real time. However, frequent software crashes and erroneous landmarks appearing “out of the blue,” requiring manual correction, were tedious. Individual section thickness, defined smoothing, and unlimited structure number could not be integrated. The reconstruction remained underdimensioned and not sufficiently accurate for this study's reconstruction problem. SeViSe permitted unlimited structure number, late addition of extra sections, and quantified smoothing and individual slice thickness; however, SeViSe required more elaborate work-up compared to SURFdriver, yet detailed and exact 3D reconstructions were created. © 2006 Wiley-Liss, Inc.