Focal segmental glomerulosclerosis (FSGS) accounts for a substantial proportion of diagnoses in children referred to pediatric nephrologists for proteinuria but is often difficult to diagnose by clinical presentation alone. We analyzed our experience with children presenting with proteinuria to determine whether age and ethnicity affect the probability of having FSGS and its risk of progression to ESRD. Age, ethnicity, duration of follow-up, clinical outcome to date, and time to ESRD (when applicable) were identified for each patient. Diagnoses were assigned based on clinical or histopathological criteria depending on whether a renal biopsy had been performed. Histopathological diagnoses superceded clinical diagnoses. Patients with proteinuria due to systemic diseases or acute glomerulonephritis were excluded. Proteinuria was the presenting symptom in 17% (237/1405) of patients in our database. The most common histopathological diagnosis was FSGS, accounting for 28% (66/237). FSGS was more common in African-Americans(AA)(46%) than non-AA (21%) (p<0.001). AA with FSGS were older at presentation (13.5 ± 3.8 years) than non-AA (6.6 ± 5.1 years)(p<0.001), and the probability of having FSGS increased with older age in AA (p<0.01). The probability of FSGS in AA was 0.50 by 12 years, and increased to 0.80 by 16 years of age. The overall% of ESRD from FSGS was 30%(20/66) during 49 months of follow-up. Although not significant, 5 year renal survival tended to be worse in AA compared to non-AA (36% vs. 58%), and the time to ESRD tended to be shorter (27 vs. 41 months). These differences in the probability of FSGS and its outcome based on age and ethnicity suggest that FSGS is expressed differently in AA compared to non-AA. If so, studies that evaluate treatment of FSGS should be stratified by age and ethnicity, since the response to treatment is likely to differ based on these factors.