Although several studies have suggested that the relationship between the various risk factors and breast cancer may differ according to the breast cancer subtypes, it is not clear whether the p53 protein expression status of breast cancer represents an etiologically distinct form of the disease with different risk factor profiles. This study was carried out to investigate whether the relationship between breast cancer and serum antioxidant vitamins would differ according to p53 expression status (p53-positive and p53-negative). Breast cancer cases (n = 92) and controls (n = 122) were recruited between January 1993 and April 1994 at the Asan Medical Center. p53 overexpression in tissue sections from 92 women with breast cancer was determined using immunohistochemistry. The serum concentrations of the carotenoids and alpha-tocopherol were measured using liquid chromatography. For serum antioxidant vitamins, odds ratios with respect to the common control group for breast cancers of different p53 protein overexpression status were compared using multiple polytomous logistic regression. Serum concentrations of beta-carotene and zeaxanthin + lutein were significantly associated with the risk of breast cancer in p53-positive and p53-negative cancers. The adjusted odds ratios for the highest compared with the lowest quartile were 0.19 [95% confidence interval (CI) = 0.01-2.51] for beta-carotene and 0.34 (95% CI = 0.06-1.87) for zeaxanthin + lutein in p53-positive cancer cases and 0.05 (95% CI = 0.00-0.57) for beta-carotene and 0.06 (95% CI = 0.01-0.40) for zeaxanthin + lutein in p53-negative cancer cases. However, none of these associations differed significantly between p53-positive and p53-negative cancers. The results of this study showed that the relationship of antioxidant vitamins with breast cancer does not differ according to the presence or absence of the p53 mutation.