Abstract: Background: Primary sclerosing cholangitis (PSC) is an uncommon disorder, rarely diagnosed in children, moreover, data on its natural history and survival are still lacking. Aim: The study was undertaken to compare clinical, laboratory and survival rates in two series of PSC: one in a pediatric group (group A) and the other in an adult population (group B). Methods: Group A included 9 patients (5 males, 4 females, mean age 10 yrs, range 7–15); group B included 28 patients (19 males, 9 females, mean age 32 years, range 19–60). The mean follow-up was 5.2 years in group A and 6.9 years in group B (range 1–14 years). ERCP and colonos-copy were performed in each case. Survival was analyzed using the Kaplan-Meier method. Results: At presentation children showed significantly higher levels of IgG and AST compared to adults (p<0.05); moreover, interface hepatitis occurred in 50% of children and in 14.2% in adults (p= ns). During follow-up the following major events occurred: oesophageal bleeding (n=2) in group A; progressive liver failure (n=6), cholangiocarcinoma (n=3), colonic cancer (n=1) in group B. Liver transplantation (OLTx) was performed in 4 adults (one died after a retransplantation). No deaths were observed in children. The Kaplan-Meier curve in adults shows a 65% rate of survival at 10 years. Conclusions: The present findings on PSC suggest a more severe activity of the disease in children than in adults at presentation; nonetheless, the prognosis seems to be better in children than in adults. The Mayo score prognostic index does not predict the development of liver/colonic cancer. A poor outcome (defined as death or being listed for OLTx) only occurred in adults.