Behçet's syndrome (BS) often presents with aphthous and genital ulcers, uveitis, and erythema nodosum. Renal involvement has been reported with most cases presenting with renal amyloidosis, IgA nephropathy, or crescentic glomerulonephritis. We describe a case of a 49-year-old woman with relapsing BS symptoms coinciding with new-onset development of nephrotic syndrome. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) that was treated with prednisone and etanercept for BS therapy. Both proteinuria and BS symptoms responded to treatment with complete remission. To our knowledge, our report is the first to show evidence of a possible connection between BS and FSGS and discusses the pathophysiologic mechanism that explains this link. .