Three germline p53 polymorphisms, a 16 bp duplication in intron 3, a Bst UI RFLP in exon 4 and Msp I RFLP in intron 6 have previously been tested for a association with Swedish breast cancer patients. The rare Bst UI allele was found to be associated with breast cancer in the Swedish patients (OR 1.47, 95% CI, 1.08-2.00). In our hospital-based case-control study leukocyte DNA of 107 breast cancer patients and 305 control women was analyzed. Individuals heterozygous at all 3 polymorphic sites (27/107) were over-represented in the breast cancer group with an age-adjusted OR of 2.01 (95% CI, 1.02-3.94). Haplotype analysis identified the 16 bp A2 allele (with 16 bp duplication) and Msp I A1 allele (loss of Msp I restriction site) as risk alleles. The results of this study suggest that the rare alleles 16 bp A 2 and Msp I A1 of the p53 locus may modify the risk of breast cancer in German women.