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Some studies have shown disproportionate cancer incidence burden in rural areas which may be attributable partly due to the use of ‘rural’ as a generic term implying homogeneity of risk/protective factors across wide geographic spans. Counties in SEER 18 registries (years 2001-2011) were classified by their Rural-Urban Continuum Code (RUCC) and aggregated into urban, adjacent rural, and non-adjacent rural and were also aggregated into 3 regions: North, South, and West. Two-way ANCOVA was performed with region and RUCC as factors with adjustment for rates of common risk factors obtained from the County Health Rankings (2013). RUCC has a significant effect on incidence rate in urban areas on breast (P =0.001) and prostate (P =0.009). Colorectal significantly varies by region (P