We report a patient who developed acute promyelocytic leukemia (APL) concomitantly with a second relapse of non-Hodgkin's lymphoma (NHL), intermediate grade, WF type E. At diagnosis and at first NHL relapse, the patient had received the same chemotherapy regimen, which included drugs targeting DNA topoisomerase II, i.e., etoposide (total dose 5,760 mg) and idarubicin (total dose 180 mg). Thirty-eight months after initial treatment, the patient showed pancytopenia associated with lymphoma recurrence. Bone marrow examination revealed the presence of atypical promyelocytes with Auer rods; cytogenetics showed t(15;17), and molecular analysis detected promyelocytic leukemia-retinoic acid receptor alpha rearrangement. APL reached complete remission after all trans retinoic acid therapy, whereas NHL did not respond to further chemotherapy. In the literature, five other patients developed APL after treatment for lymphoma, from a total of 59 patients developing sAPL after treatment for any type of neoplasia.