The sequential occurrence of Langerhans cell histiocytosis and acute leukemia in only one individual has been reported previously; however, it is rarely observed that Langerhans cell histiocytosis can transform into acute lymphoblastic leukemia, and the underlying mechanisms remain unclear. In this report, we have analyzed a case of acute lymphoblastic leukemia converted from Langerhans cell histiocytosis using high-throughput sequencing method, and found that mitogen-activated protein kinase gene mutation, which can act as a marker for poor prognosis, might be involved in disease transformation. This is the first description about acute lymphoblastic leukemia B-cell type after Langerhans cell histiocytosis diagnosis and therapy in China.