Attempts to find genes contribution to complex diseases, such as cancer, require new study designs which incorporate an efficient use of population resources and modern genotyping technologies. We describe here two approaches, used by us for the study of breast cancer, both of which take the use of biobanks. One uses a cancer registry as a source of case information, which is then linked to a biobank on blood DNA. The biobank provides also samples from matched controls. After genotyping, clinical data are retrieved from hospital records, and the results can be presented for genotype-specific cancer risks, or similarly for genotype-specific clinical and survival parameters. The second approach uses registered data on cancer in families or among twins. On defined groups of patients, paraffin tissue is collected by contacting the pathology departments of the hospitals where the patients were diagnosed. Tumor and healthy tissue is prepared and used for mutation, the loss of heterozygosity, or copy number analysis. We believe that in the era of whole-genome genotyping technologies, the importance of well-characterized sample sets cannot be overemphasized. Samples rather than technologies limit the rate of gene discovery in complex diseases.