Purpose The purpose of this study was to examine the geographic variations of late‐stage diagnosis in colorectal cancer (CRC) and breast cancer as well as to investigate the effects of 3 neighborhood‐level factors—socioeconomic deprivation, urban/rural residence, and spatial accessibility to health care—on the late‐stage risks. Methods This study used population‐based South Dakota cancer registry data from 2001 to 2012. A total of 4,878 CRC cases and 6,418 breast cancer cases were included in the analyses. Two‐level logistic regression models were used to analyze the risk of late‐stage CRC and breast cancer. Findings For CRC, there was a small geographic variation across census tracts in late‐stage diagnosis, and residing in isolated small rural areas was significantly associated with late‐stage risk. However, this association became nonsignificant after adjusting for census‐tract level socioeconomic deprivation. Socioeconomic deprivation was an independent predictor of CRC late‐stage risk, and it explained the elevated risk among American Indians. No relationship was found between spatial accessibility and CRC late‐stage risk. For breast cancer, no geographic variation in the late‐stage diagnosis was observed across census tracts, and none of the 3 neighborhood‐level factors was significantly associated with late‐stage risk. Conclusions Results suggested that socioeconomic deprivation, rather than spatial accessibility, contributed to CRC late‐stage risks in South Dakota as a rural state. CRC intervention programs could be developed to target isolated small rural areas, socioeconomically disadvantaged areas, as well as American Indians residing in these areas.