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Context: The occurrence of second malignancies is not rare in children treated for primary tumors. Objectives: The aim of this study was to investigate the occurrence and the outcomes of second malignancies in children and adolescents from a large tertiary pediatric hematology-oncology center. Materials and Methods: A retrospective study was performed looking into the characteristics and outcomes of second malignant neoplasms in children and adolescents treated for primary malignancies in a single center over a 15-year period. Results: Among 270 children and adolescents treated for hematological malignancies and solid tumors from 2000 to 2015, five cases of second malignancy were diagnosed including cancer of the parotid gland, renal cell carcinoma, Hodgkin's lymphoma, thyroid carcinoma, and transitional liver cell carcinoma in patients previously treated for acute myeloid leukemia, glioblastoma multiforme, B-acute lymphoblastic leukemia, Langerhans cell histiocytosis, and medulloblastoma, respectively. Primary malignancies were treated with chemotherapy in all cases and four out of five patients had also received radiotherapy. Mean age at diagnosis of second malignancy was 10 years and 4 months. Overall survival after diagnosis of second malignancy was 80% at 12 months and 75% at 5 years. Conclusions: Close surveillance and long-term follow-up are mandatory for the identification of late effects in children treated for malignancy. [ABSTRACT FROM AUTHOR]