All urologists have faced patients suffering a renal cancer asking for the occurrence of the disease in their offspring and very often the answer to this question has not been well founded from the scientific point of view, and only in few cases a familial segregation tree is performed. The grate shift seen in the detection of small renal masses and renal cancer in the last decades will prompt us to know the indications for familial studies, which and when are necessary, and probably to refer those patients with a suspected familial syndrome to specialized oncological centers where the appropriate molecular and familial studies could be done. Use of molecular genetic testing for early identification of at-risk family members improves diagnostic certainty and would reduce costly screening procedures in at-risk members who have not inherited disease-causing mutations. This review will focus on the molecular bases of familial syndromes associated with small renal masses and the indications of familial studies in at-risk family members.