Colorectal cancer (CRC) is the third-leading cause of cancer deaths in the United States. There is a disparity in CRC cases, with blacks having a higher incidence and mortality than whites. The cause of these disparities is a mixture of socioeconomic, dietary, lifestyle, and biological factors. The role of biology in causing these disparities is largely unknown. Studies have shown that immune cell infiltration into the tumor can be used as prognostic factors in CRC and other cancers. Many of these studies focus on cytotoxic T lymphocytes, but other cells exist that possess antitumorigenic properties. One of these types of cells is natural killer (NK) cells, which are both cytotoxic and capable of secreting IFN-_. The goal of this study is to elucidate the role of the immune response—specifically, NK cells—in the prognostic disparities observed in colon cancer based on race, gender, and infiltration of CD8+ T lymphocytes. Formalin-fixed paraffin-embedded archival colon cancer tissue slides were obtained from the North Carolina Colon Cancer Study (NCCCS), a population-based cohort (45% black, 55% white). Immunohistochemistry (IHC) was used to detect the presence of CD57+ cells, and the mean numbers of intraepithelial and intratumoral cells were quantified by two independent observers from three high-powered fields (HPF; 100x total magnification). Tumors from 126 different patients in the NCCCS, culled from the top and bottom quartiles for CD8+ cell infiltration and chosen to as equally represent blacks/whites and males/females as possible, were analyzed by IHC. The Mann-Whitney U test was employed for statistical analysis. No significant difference was found between blacks and whites using both intraepithelial and intratumoral CD57+ cell counts, but a significant difference was observed between males and females using intratumoral CD57+ cell counts (p<0.05). Additionally, a highly significant difference in CD57+ cell infiltration was found between high- and low-CD8+ cell infiltrating patients (both p<0.001). These data indicate some degree of immune coordination between CD8+ and CD57+ cells. The basis of this immune coordination depends on the identity of the CD57+ cells, but may include cytotoxic T lymphocytes and/or NK cells (either in a cytotoxic capacity or by secretion of IFN-_). Further investigation into the identity and function of the CD57+ cell infiltrate are needed. Additionally, our data suggest—but do not completely rule out the possibility—that NK cells are not involved in the observed racial disparities in colon cancer. Furthermore, the data do not eliminate the possibility that other immunological factors are involved in contributing to the racial disparity.