The goal of indirect molecular diagnostic techniques is the detection of a link between a specific allele of a polymorphic genomic marker and a given disease. This technique is used in two specific clinical situations: 1) when the gene is unknown and the search for a mutation or a gene product is impossible 2) when the gene is known but large and several mutations might be present. If none of the known mutations prevails in the local population the systematic and sequential search for every single mutation is not economical. A linkage study is required in those instances. The indirect analysis was up to the nineties based on markers detecting DNA-restriction fragments of various length. By the amplification of microsatellites by PCR the indirect approach has brought enormous progress. Together with the mapping by the Human Genome Project it will progress further. Although indirect molecular methodology can often avoid extended work it is only applicable to families with a member already affected by the disease. DNA from this individual is needed for the detection of a link of one allele to the disease. This means necessarily that the disease must be inherited and that the diagnosis is certain. Presymptomatic molecular diagnosis is illustrated by the analysis of a pedigree with familial adenomatous polyposis by microsatellite PCR techniques.