Congenital and infant acute leukemia remain one of the most puzzling clinical issues in pediatric hematology-oncology. There is a paucity of studies focused on these rare, aggressive, acute leukemias; specifically, there is little study on the differences in disease in the youngest of infants less than 1 year of age unlike the numerous studies of the disease in older children. The United States National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer population registry program has been integral for a plethora of clinical population and pathology research studies for numerous diseases in the last 40 years and has an excellent resource for investigation of the infant population. Laboratory medicine and pathology professionals must use pathology results not only to diagnose individuals after the disease has been discovered, but the information must be applied retrospectively to develop new testing strategies. By classifying the intense heterogeneity within these cancers, the distinct changes of the diseases within individuals can be established, ultimately reshaping diagnostic methodologies. Through the application of Integrative Molecular Pathological Epidemiology to a 325-infant case series from the SEER program from 2008 to 2014, this dissertation study was used to evolve the classification of these pediatric cancers with the application of scientific nosology. This dissertation study has documented characteristics of this population for application in further precision medicine investigations to influence laboratory medicine algorithms for diagnosis and management of patients guiding health policy that are aimed at improving outcomes in the youngest of children