This chapter provides an overview of acute leukemia, lymphoma and bone tumors. Leukemia can present with myriad of symptoms from pallor to life-threatening tumor lysis syndrome. A high index of suspicion in patients presenting with the following features can help to diagnose leukemia early. The diagnosis of leukemia needs a bone marrow aspiration with special studies including cytochemistry and immunophenotyping to characterize the leukemia. The subclassification of acute lymphoblastic leukemia (ALL) as pre B, mature B or T cell type is done on by immunophenotyping using flow cytometry which characterizes the antigens on the surface of the blasts. Modern antileukemia therapy uses risk stratification to decide the chemotherapy regimens to be used in any given patient. The successful management of acute leukemia in children involves largely two components: specific antileukemia therapy and supportive care. Infection, bleeding, anemia, hyperleukocytosis and tumor lysis syndrome are the most common complications encountered at the time of diagnosis of acute leukemia. Acute lymphoblastic leukemia (ALL) is treated with intensive chemotherapy for 6 months followed by 2–3 years of oral maintenance therapy. Lymphoma is called the great mimic as its symptoms can be confused with a host of other illnesses. Awareness of its varied presentations helps the clinician to suspect it early and prevent complications due to delayed diagnosis. Clinically, enlarged lymph nodes are the most common presentation of lymphoma in children. Fine needle aspiration cytology (FNAC) is not a reliable test when suspecting malignancy and should not be used to rule our malignancy. Lymphomas can present with other symptoms which may or may not be associated with peripheral lymphadenopathy. Once lymphoma is suspected, a biopsy should be performed at the earliest. Staging of Hodgkin and non-Hodgkin lymphoma (NHL) is different as Hodgkin lymphoma spreads in a contiguous fashion. Osteosarcoma and Ewing\'s sarcoma are the commonest malignant bone tumors in children. Non-Hodgkin lymphoma of the bone is uncommon but should be considered in the differential diagnosis. Diagnosis of malignant bone tumors needs an open biopsy unless it is a deep seated tumor as in arising from the pelvic bone. The biopsy should be performed by an experienced surgeon who will perform the definitive surgery later on.