Renal cystic disease (RCD) represents an important and leading cause of end-stage renal disease in children. RCD can be acquired or inherited, and when associated with extra-renal manifestations, often occurs as part of a well-defined syndrome. We have studied the clinical phenotypes of 105 children with RCD (45 of them had extrarenal manifestations). The most common disorders were nephronophthisis and related ciliopathies (36.2%), polycystic kidney disease (31.4%) and multicystic dysplastic kidneys (19%). Four syndromic cases were unclassified, not being previously reported. Abdominal ultrasonography was the most helpful diagnostic test, while CT scan, renal biopsy and investigations for extrarenal manifestations were required in selected cases. We propose an algorithm for diagnostic approach to patients with RCD.