Hereditary cancer syndromes are characterized by increased risk of cancers but other symptoms can also be seen. Germline mutations usually cause a high cancer risk but more moderate risk genes are being identified. A negative mutation screening cannot exclude a hereditary cancer syndrome, since it is not possible to analyse all genes. Genetic diagnostics are now part of clinical management and new technology such as next generation sequencing and high-throughput screening are being implemented in clinical settings. This will also impose new challenges such as identification and interpretation of mutations with unknown significance.