This chapter describes acute lymphoblastic leukemia or lymphoma (ALL), mature T- and B-cell leukemias. Clinical features include lethargy, fever, infection, bleeding, joint pain (typical early complaint from children), organomegaly, and cytopenia. About 75% of ALL patients are under six years of age, and most patients are between 2–10 years old. This chapter covers the WHO classification of precursor lymphoid neoplasms, comparison of immunophenotype, cytochemistry and gene rearrangements of B- and T-ALL, B-lymphoblastic leukemia or lymphoma (B-ALL), cytogenetic translocations and associated molecular abnormalities of ALL, cytogenetics and associated clinical prognosis of ALL, differential diagnosis of ALL, mature b-cell leukemia, hairy cell leukemia (HCL), and mature t-cell leukemia and natural killer celllarge granular lymphocyte leukemia (NK-LGLL).