Percutaneous guided liver biopsy (PLB) is the standard procedure for obtaining hepatic tissue for histopathological examination, and remains an essential tool in the diagnosis and management of the exact pattern and extent of parenchymal liver diseases. This a prospective hospital based study was conducted during the period from April 2008 till June 2010 at Pediatric Department of Assiut University Hospital and Pediatric and Pathology Department of Sohag University Hospital, Upper Egypt aiming to highlight the diagnosis and outcome of the unexplained enlarged liver in children by PLB. The study included 42 children who fulfilled inclusion criteria which were: age range 8 months to 10 years, unexplained hepatomegaly and or hepatosplenomegaly, and suspected cases of metabolic liver diseases. Exclusion criteria were: age < 8 months or > 10 years, patient with acute or chronic viral hepatitis, patients with proved fulminant hepatitis, localized liver masses, liver cell failure, chronic hemolytic anemia, suspected biliary atresia, primary or secondary liver tumors, and cardiac causes of hepatomegaly. PLB had been performed to all cases under ultrasonographic guide; 28 (66.7%)  of the studied cases were diagnosed by PLB, while in 14 (33.3%) cases, we could not reach a definitive diagnosis and were labeled as idiopathic liver diseases which was the commonest diagnosis, followed by storage and metabolic diseases (28.5%), congenital hepatic fibrosis (CHF) (11.9%), fatty liver (9.6%), hepatic ven-occlusive disease (VOD (9.6%), and hepatic bilharziasis (7.1%). Two cases (4.7%) suffered of major postoperative complications (hemobilia), while persistent postoperative pain was present in 8 (19.1%) cases. After one year follow up of those children; 15 cases (33.7%) died, 6 (14.2%) cases missed follow up, 9 (21.4%) were treated from parenchymal liver cell failure and 12 (28.5%) cases showed a stationary course. The study concluded that PLB is a useful and practical tool for the appropriate diagnosis of pediatric liver diseases. The procedure is suitable to be performed safely on an outpatent basis after fulfilling the prerequisite of liver biopsy