Situs inversus totalis is a rare congenital anomaly that often occurs concomitantly with other disorders. A spectrum of renal abnormalities of patients with situs inversus has been reported. Developmental anomalies, including agenesis, dysplasia, hypoplasia, ectopia, polycystic kidney, and horseshoe kidney, have been reported. The association of situs inversus with nephrotic syndrome is very rare. We report the first known case of situs inversus totalis with nephrotic syndrome caused by primary focal segmental glomerulosclerosis, and the possible mechanism of this association.