The database design and diverse application of NLCD 2001 pose significant challenges for accuracy assessment because numerous objectives are of interest, including accuracy of land-cover, percent urban imperviousness, percent tree canopy, land-cover composition, and net change. A multi-support approach is needed because these objectives require spatial units of different sizes for reference data collection and analysis. Determining a sampling design that meets the full suite of desirable objectives for the NLCD 2001 accuracy assessment requires reconciling potentially conflicting design features that arise from targeting the different objectives. Multi-stage cluster sampling provides the general structure to achieve a multi-support assessment, and the flexibility to target different objectives at different stages of the design. We describe the implementation of two-stage cluster sampling for the initial phase of the NLCD 2001 assessment, and identify gaps in existing knowledge where research is needed to allow full implementation of a multi-objective, multi-support assessment. ?? 2008 American Society for Photogrammetry and Remote Sensing.