A 5-year-old African-American male was diagnosed with nephrotic syndrome (NS). Because of concomitant leukopenia, bone marrow aspiration was performed, which did not demonstrate a hematological malignancy. The patient received standard daily steroid therapy for treatment of NS. Steroid resistance at 5 weeks of therapy led to a renal biopsy, which documented focal segmental glomerulosclerosis (FSGS). He was begun on cyclosporin A (CsA) and later switched to tacrolimus because of side-effects of CsA. Seven months after the initial diagnosis of NS, the patient was diagnosed with acute lymphoblastic leukemia (ALL). The patient is in complete remission of ALL and partial remission of NS with continued nephrotic-range proteinuria. Review of the literature shows four other cases of pediatric ALL after NS. No particular immunosuppressive agent seemed to be causative in the evolution of ALL. Although the exact mechanism for development of ALL after NS is unknown, the incidence of leukemia may be increased after immunosuppressive therapy when used in this context.