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There is an increasing need for new methods and tools that support knowledge construction from complex geospatial datasets related to public health. This study is part of a larger effort to develop, implement, and test such methods and tools. To be successful, the design of methods and tools must be grounded in a solid understanding of the work practices within the domain of use; the research reported here focuses on developing that understanding. We adopted a user-centered approach to toolset design where we investigated the work of cancer researchers and used the results of that investigation as inputs into the development of design guidelines for new geovisualization and spatial analysis tools. Specifically, we conducted key informant interviews focused on use, or potential use, of geographic information, methods, and tools and complemented this with a systematic analysis of published, peer-reviewed articles on geospatial cancer research. Results were used to characterize the typical process of analysis, to identify fundamental differences between intensive users of geospatial methods and infrequent users, and to outline key stages in analysis and tasks within the stages that methods and tools must support. Our findings inform design and implementation decisions for visual and analytic tools that support cancer prevention and control research and they provide insight into the processes used by cancer researchers for addressing the challenges of geographic factors in public health research and policy.