The authors report a long-term (over 22 years) follow-up of four familial cases, 1 brother and 3 sisters, affected by classic Caroli's disease. The male patient experienced acute cholangitis at the age of 6 and 1 of the 3 sisters at 12 years. The other two sisters were asymptomatic at the time of diagnosis. At the last control, all the patients were alive and have remained symptom-free for more than 22 years. Nevertheless, some data suggest a slowly evolving impairment of the disease even in the absence of a clinical expression. In this paper, the ways in which Caroli's disease is inherited and managed are also discussed.