Hispanic women differ from non-Hispanics in breast cancer incidence, stage at diagnosis, and survival. Ethnic differences in genetic makeup, reproductive patterns, diet, socioeconomic status, physical activity, and other unidentified cultural factors may be responsible for the disparity. This study investigated occurrences of p53 tumor suppressor gene mutations in South Florida white Hispanic and white non-Hispanic women with primary breast cancer. Tumor tissues were obtained from a consecutive series of women with breast cancer who underwent breast resection at the Jackson Memorial Hospital, Miami, Florida between 1984 and 1986. A total of 231 women with primary breast cancer, aged 31-85 years, were included in the study. Among them, 64 (27.7%) were white Hispanic and 167 (72.3%) were white non-Hispanic. The majority of the patients were white non-Hispanics (72.3%). Compared to white non-Hispanics, however, white Hispanics had significantly higher proportions of tumors larger than 2 cm (53.1% v.s. 28.7%, p = 0.00) as well as larger tumor size at diagnosis (mean: 4.2 v.s. 3.0 cm, p = 0.00). The p53 gene mutation rate was significantly lower in white Hispanics than in white non-Hispanics (51.6% v.s. 70.7%, p = 0.01). Furthermore, among node-negative breast cancer patients, after adjustment for tumor size at diagnosis, logistic regression results showed that white Hispanics were 71% less likely than white non-Hispanics to carry p53 mutations (OR = 0.29 and 95% CI = 0.09-0.91). We conclude that white Hispanic women with breast cancer might have lower p53 gene mutation prevalence than white non-Hispanic women.