Precursor lymphoid neoplasms, encompassing lymphoblastic lymphoma/leukemias of B- and T-lineage are the most common type of childhood cancer. B-lymphoblastic neoplasms include >20 clinically significant molecular/genetic subtypes, which are relatively similar at the morphologic and immunophenotypic level. While the complex genetics of T-lymphoblastic neoplasms are well-characterized, they are not currently used for their pathologic subclassification. The overall cure rate of lymphoblastic neoplasms exceeds 90%, although outcome remains dismal for some disease subtypes. Effective treatment requires correct risk stratification (which involves disease features, particularly the genetic subtype, patient-specific features, including pharmacogenetics, and the level of residual disease in response to initial therapy), as well as minimal residual disease monitoring by various laboratory methods at specific timepoints during therapy. Therapy modalities include combination chemotherapy, tyrosine kinase inhibitors, monoclonal antibodies, and, for very high-risk, relapsed, or refractory disease, hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapies. This chapter will focus on the pathologic features of these neoplasms as they pertain to diagnosis, disease monitoring, and detection of relapse, in the context of modern diagnostic methodologies and therapy modalities.