<p>Rare tumours are variously defined but usually affect not more than 1 in 100000 people. They can be present at birth, in childhood or later in life. The diagnosis of a rare tumour can sometimes point to an underlying hereditary condition, and one should take into account important considerations that can increase suspicion of a genetic cause of the disease. While some rare neoplasms are highly specific of a hereditary tumour susceptibility syndrome (and can be almost pathognomonic), thus prompting a direct genetic evaluation, most rare neoplasms may appear within the context of multi-tumour susceptibility syndromes, and here they add important weight to the global assessment when considering a genetic referral. Despite their low frequency, novel associations between rare neoplasms and hereditary conditions continue to emerge, although a solid association is often lacking. On the contrary, some infrequent tumours are nearly always non-hereditary (sporadic) in nature. Of note, the definition of rare tumours should be age-adjusted as paediatric tumours are by definition rare when compared with adult tumours in absolute terms. Therefore, in this review, in the paediatric section, we focus on tumours that occur rarely in childhood. This can include cancers that typically occur in adults, but in this case, it appears in a child. Both situations are a strong indication for genetic testing. In this review, we described different scenarios in which rare neoplasms can serve as indications (or not) for an underlying inherited cancer susceptibility.</p>