Dr. Jaffe completed her medical education at Cornell University and the University of Pennsylvania, receiving an M.D. from the latter in 1969. After an internship at Georgetown University, she joined the NCI as a resident in anatomic pathology, and has been a senior investigator since 1974, focusing on the classification and definition of lymphoid neoplasms. She has served on the editorial boards of The American Journal of Pathology, The American Journal of Surgical Pathology, Blood, Cancer Research, and Modern Pathology, among others. She has been president of both the Society for Hematopathology as well as the United States and Canadian Academy of Pathology, and was elected to the advisory board of the American Society of Hematology. In 1993, she was elected a fellow of the American Association for the Advancement of Science, and in 2005 was Chair of the Medical Sciences Section of AAAS. She was among the 10 most highly cited researchers in clinical medicine for the field of oncology between 1981 and 1998. Among her awards are the Fred W. Stewart Award from Memorial-Sloan Kettering Cancer Center, the Mostofi Award from the United States and Canadian Academy of Pathology, and the Distinguished Clinical Teacher Award from the NIH Fellows Committee. In 2007 she was the second Anita Roberts Lecturer, recognizing women in science at the NIH. She was awarded the Honoris Causa from the University of Barcelona in 2008, and received the Chugai Award for Excellence in Mentoring and Scholarship from the American Society of Investigative Pathology. In 2008 she was elected to the Institute of Medicine of the National Academies. Dr. Jaffe was awarded the Henry M. Stratton Medal from the American Society of Hematology in 2013. 

Cancer Biology, Clinical Research, Genetics and Genomics, Immunology