BackgroundGeographic information system (GIS)-based health studies require information on the physical location of data points, such as subject addresses. In a study of California women diagnosed with breast cancer between 1988 and 1997, we needed to locate the residential addresses of 4,537 women with post office boxes (POBs)MethodsWe investigated the feasibility of tracing street addresses for the POBs and examined potential selection biases and case attribute misclassifications introduced by different methods of handling POBs in GIS-based health studies.ResultsOur tracing method yielded street addresses for only 34% of POBs in our study. Examination of subjects’ case characteristics revealed that boxholders were not representative of the full population. Geocoding using a POB’s delivery-weighted five-digit zip code centroid, as a proxy for street address, resulted in case attribute misclassification for 81% of boxholders.ConclusionsDisease registries should modernize their infrastructure to complement GIS technologies. Epidemiologists should understand GIS data limitations and consider potential biases introduced by incomplete or inaccurate geocoding.