A significant survival difference between black and white breast cancer patients has been observed in the United States. Evaluation of the prognostic value of DNA ploidy and S-phase fraction (SPF) in black and white breast cancer patients may contribute to our understanding of the mechanisms of racial disparity in survival. A sample of 98 patients (50 blacks and 48 whites) who participated in the Black/White Cancer Survival Study was selected for DNA flow cytometry analysis. Patients were followed between 4.5 and 6.5 years. The impacts of DNA ploidy and SPF on breast cancer survival were examined. Kaplan-Meier survival curves, log rank statistics, and Cox proportional hazards regression were used for survival analyses. Black patients were more likely than white patients to have tumors with high SPF (P < 0.05), but there was no difference in DNA ploidy (P = 0.79). Because there were significant interactions of both DNA ploidy and SPF with race, survival was examined separately for blacks and whites. Significantly poorer survival was observed for white patients with class A ploidy (hypodiploidy, hypotetraploidy, and hypertetraploidy; P = 0.001) and with high SPF (P = 0.025). The elevated hazard ratios remained significant after adjusting for age and stage. Further adjustment for adjuvant therapy and histopathological characteristics of tumor reduced the hazard ratios of SPF to a nonsignificant level. No significant associations were found between survival and DNA ploidy or SPF among blacks. DNA ploidy and SPF are prognostic factors for breast cancer survival in white patients but not in blacks. This may have clinical implication in breast cancer management.