A considerable proportion of the familial aggregation of breast cancer is probably due to alleles of low penetrance. Although their contribution to risk is relatively small, they can contribute to a large proportion of breast cancer cases in the population, because the risk-conferring alleles of these genes are common. The candidate gene approach is one of the most logical and practical strategies to identify these risk-enhancing, low-penetrant variants. A major obstacle in investigating the risk associated with multiple candidate genes has been the lack of large-scale genotyping technologies. Recently developed microarray and matrix-assisted laser desorption–ionization time-of-flight (MALDI-TOF) mass spectrometry technologies are ideally suited to the problem of high-throughput genotyping. We are relying on the power of these techniques to carry out a population-based breast cancer case-control study for 32 single-nucleotide polymorphisms (SNPs). We selected these SNPs from genes of crucial pathways that are frequently perturbed in cancers, such as those governing the cell cycle, carcinogen metabolism and the immune response pathways. We are currently developing both microarray and MALDI-TOF mass spectrometry techniques so that both can use the primer extension method to detect the allelic variants of SNPs. Both techniques are used in combination on a panel of cases involving several SNPs, to assess specificity and reproducibility. The combination of both methods will be a powerful tool for genotyping a large number of SNPs in a large number of cases. Advances in our knowledge of disease etiology will significantly expand our abilities to design strategies for the prevention of breast cancer development and the inhibition of its progression.