Klippel-Trenaunay syndrome (KTS) is a congenital malformation syndrome involving blood and lymph vessels and disturbed growth of bone and soft tissues. The clinical presentation can be extremely variable. An extensive literature search showed that various authors used many different diagnostic criteria. Uniform diagnostic criteria are an absolute prerequisite for successful molecular studies and for comparisons between various studies on almost any aspect of the disorder. Based on data from 3 unusually experienced colleagues and our experience, we propose restrictive diagnostic criteria, which still respect the extremely variable nature of KTS. Important aspects are that growth can be both increased and decreased, very small arteriovenous fistula can be present, and varicosities do not need to be present. Several hypotheses regarding cause and pathogenesis in KTS exist, but none explains all KTS characteristics completely. We propose yet another hypothesis which is at variance with the hypothesis of paradominant inheritance.