The article presents the features of the clinical manifestation of multiple primary sporadic and heritable malignant tumors in 104 children who observed at Pediatric Oncology and Hematology Research Institute of «NN Blokhin's National Medical Research Center of Oncology» from 1998 to 2012. The age of patients at the time of occurrence of the second malignant tumor ranged from 2.8 to 28 years and averaged 15.6 years. The second neoplasia occurred significantly more frequently in the group of primary hemoblastosis, compared with the group of solid tumors - 8.7% versus 3.4%, respectively (p <0.0001). In children with multiple primaries, were found tumors that occur in common the most frequency. Retinoblastoma patients have an increased risk of developing sarcoma. Patients with Hodgkin's lymphoma have an increased risk of developing leukemia. In surviving children after treatment of the first neoplasia the thyroid, bone tissue and breast have a specific risk for the development of metachronous cancer and are target organs for control. Children with new hematopoietic tumors may be candidates for metachronous development of leukemia and bone tissue tumors. The using methods Next Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) revealed germinal mutations in 12 children with of multiple primary tumors. The mutations in the TP53, RB1, CHEK2, FANCN/PALB2, MLH1, PMS2 genes identified in patients were associated with hereditary syndromes and an increased risk of developing second tumors, among which: sarcomas, brain tumors, hematopoietic tumors were the most frequent. It was shown that the second tumors can appear at the any age. Children who survived the treatment of the first tumor in later life should be monitored annually. Clinical management of children with multiple primary tumors requires a multidisciplinary approach.