BACKGROUND: This retrospective case series aimed at exploring the optimal urinary protein-to-creatinine ratio (uP/uCr) cut-off value to determine the need for renal biopsy in pediatric patients with isolated asymptomatic proteinuria (ASP). METHODS: Data from 32 patients (16 boys, 16 girls) with persistent isolated ASP treated between January 2001 and September 2010 were analyzed. The uP/uCr cut-off value at which a renal biopsy is indicated was determined using the minimum p-value approach. An "optimal" cut-off value was selected to distinguish significant and non-significant glomerular changes. RESULTS: The minimum p-value approach using the χ2-test resulted in a peak uP/uCr of 0.5 g/g x Cr, which was then used to divide the patients into a low-proteinuria group and a high-proteinuria group. The proportion of significant glomerular changes was marginally higher (p = 0.097) in the high-proteinuria group than in the low-proteinuria group after adjustment for multiple tests. In addition, the number of patients with severe proteinuria at the most recent followup was higher in the high-proteinuria group than in the low-proteinuria group. CONCLUSION: The use of a uP/uCr >= 0.5 g/g x Cr may be a reasonable criterion for renal biopsy aimed at distinguishing renal outcomes in patients with persistent isolated ASP.