This volume constitutes the refereed proceedings of the 12th International Workshop on Combinatorial Image Analysis, IWCIA 2008, held in Buffalo, NY, USA, in April 2008. The 28 revised full papers and 10 revised poster papers presented were carefully reviewed and selected from 117 initial submissions. The papers are organized in topical sections on digital geometry and topology, curves and surfaces, combinatorics in digital spaces: lattice polygons, polytopes, tilings, and patterns, image representation, segmentation, grouping, and reconstruction, applications of computational geometry, integer and linear programming to image analysis, fuzzy and stochastic image analysis, parallel architectures and algorithms, grammars and models for image or scene analysis, as well as discrete tomography, medical imaging, and biometrics.