This study aimed to determine effective factors on geographic distribution of the Incidence of Colorectal Cancer (CRC) in Tehran, Iran using Geographically Weighted Poisson Regression Model. This ecological study was carried out at neighborhood level of Tehran in 2017-2018. Data for CRC incidence was extracted from the population-based cancer registry data of Iran. The socioeconomic variables, risk factors and health costs were extracted from the Urban HEART Study in Tehran. Geographically weighted Poisson regression model was used for determination of the association between these variables with CRC incidence. GWR 4, Stata 14 and ArcGIS 10.3 software systems were used for statistical analysis. The total number of incident CRC cases were 2815 in Tehran from 2008 to 2011, of whom, 2491 cases were successfully geocoded to the neighborhood. The median IRR for local variables were : unemployed people over 15 year old (median IRR: 1.17), women aged 17 years or older with university education (median IRR: 1.17), women head of household (median IRR: 1.06), people without insurance coverage (median IRR: 1.10), households without daily consumption of milk (median IRR: 0.85), smoking households (median IRR: 1.07), household's health expenditure (median IRR: 1.39), disease diagnosis costs (median IRR: 1.03), medicines costs of households (median IRR: 1.05), cost of the hospital (median IRR: 1.09), cost of medical visits (median IRR: 1.27). The spatial variability was observed for most socioeconomic variables, risk factors and health costs that had effects on CRC incidence in Tehran. Spatial variability is necessary when interpreting the results and utterly helpful for implementation of prevention programs.