A method has been developed to determine the optimal linkage key for record linkage between the cancer registry and a large-scale prospective cohort study in the Netherlands. The proposed linkage procedure is a two-stage process in which the initial computerized linkage using a particular linkage key is followed by visual inspection with additional information to separate the computer matches into true and false positives. In the determination of the optimal key, both informativeness and susceptibility to error of personal identifiers were taken into account. The performance of the various keys in the linkage was expressed in terms of sensitivity and predictive value of a reported computer match. The key, consisting of date of birth, first four characters of the family name and gender was the optimal choice, with a sensitivity of 98% and an initial predictive value of a computer match of 98%. When additional information on migration, place of birth and first initial was collected in the second stage, it was possible to eliminate the false positives from the reported computer matches without loss of true positives. Thus, the sensitivity remained constant whereas the secondary predictive value of accepted matches was maximized.