This chapter presents a state of the art summary of mature B-Cell neoplasms to its definition, biology, epidemiology, disease mechanisms, clinical signs, diagnosis, treatment and prognosis. Tumors of the hematopoietic and lymphoreticular systems consist of two main categories: myeloid neoplasms and acute leukemia and mature lymphoid, histiocytic, and dendritic neoplasms. Patients with mature B-cell neoplasms often display painless swelling of lymph nodes, persistent chills/fever, night sweats, unexplained weight loss, lack of energy, and itching. Diagnosis of mature B-cell neoplasms requires clinical, laboratory radiologic. Treatment options for mature B-cell neoplasms include chemotherapy, radiation therapy, biologic therapy, bone marrow or stem cell transplantation, and surgery. Patients with indolent forms of mature B-cell neoplasms may not require treatment until signs of progression start to cause problems. Treatment may work initially but become ineffective next time. Therefore, new or experimental treatment options need to be considered.