Phototherapy has been a useful therapeutic option for treating the neonatal indirect hyperbilirubinemia. Kernicterus is a neurologic syndrome resulting from the deposition of indirect hyperbilirubinemia in the basal ganglia and brainstem nuclei and causes a wide range of neurologic signs and symptoms such as hypotonia, hypertonia, and seizure in acute phase and different types of movement disorders in chronic phase. After the introduction of intensive phototherapy use for the treatment of neonatal indirect hyperbilirubinemia, the prevalence of kernicterus has had a marked reduction. However, concern has arisen about the risk of cancer development in the future among children who had phototherapy. Several studies tried to examine the hypothesis of the carcinogenic effect of the phototherapy. Currently, present evidence on potential carcinogenic effects of this therapy is conflicting, and there is still a lack of agreement in regard to the risk of developing cancer in children undergoing phototherapy. However, hematological cancer, especially leukemia, and skin cancer are the most mentioned cancers following phototherapy. This chapter provides a comprehensive review of current findings and suggested pathophysiological mechanisms through which phototherapy will cause cancer.