Background: Low socioeconomic status (SES) has been associated with abnormal expression of p53 in breast cancer, but this relationship has not been evaluated for colorectal cancer (CRC). A cohort of CRC patients was evaluated to determine if SES is associated with abnormal p53 expression. Methods: The study population consisted of 249 patients who underwent curative or palliative resections for CRCs at the University of Alabama at Birmingham Hospital. Measures of SES and potential confounders were abstracted from medical records. Abnormal nuclear accumulation of p53 (p53nac) was measured in CRCs by immunohistochemistry. Logistic regression was used to assess the relationship between low SES and p53nac. Results: Over half (56.2%) of the patients exhibited p53nac in their CRCs. After adjustment, the odds ratio for p53nac was 1.28 (95% CI =0.55, 2.99) for Medicaid patients relative to those without Medicaid coverage. There was no association between the prevalence of p53nac and unemployment, private insurance coverage, or having Medicare due to disability. Conclusions: The odds of having p53nac were 1.28 times higher for patients with Medicaid coverage, although these findings were not statistically significant. The results of this pilot study, however, provide evidence of a molecular basis for the decreased survival of low SES patients with CRC. © Pioneer Bioscience Publishing Company.