Cancer predisposition syndromes affecting children are rare. One can estimate that only 10% of all childhood cancers are related to predisposition. The identification of these syndromes remains important for the care of an affected child and relatives. If most of the known cancer predisposition syndromes are linked to a dominant inheritance associated with a high risk of cancer, new syndromes associated with complex inheritance are being identified. Diagnosis of a childhood cancer associated with early-onset or multiple lesions, or a malformation syndrome, or a positive family history of cancer should raise an alarm of a cancer predisposition syndrome.