A native of Lynn, Massachusetts, Dr. Weiss earned her A.B from Wellesley College and her M.D. from the Johns Hopkins School of Medicine. Following housestaff training at the Johns Hopkins Hospital and a brief tenure on the faculty, she joined the staff of the Armed Forces Institute of Pathology (AFIP), eventually becoming the Chair of the Department of Soft Tissue Pathology. During those 13 formative years at the AFIP, she co-authored with Franz Enzinger the now iconic textbook, Soft Tissue Tumors, now in its 6th edition. Subsequent academic appointments included the A. J. French Professor and Director of Anatomic Pathology at the University of Michigan and Professor and Vice Chair of Pathology at Emory University. In addition, she served as the Associate Dean for Faculty Affairs at the Emory University School of Medicine.

Over her career she has published extensively and lectured widely on all aspects of soft tissue tumors. She is known especially for her work on prognostic factors in undifferentiated pleomorphic sarcoma (formerly malignant fibrous histiocytoma), dedifferentiation in liposarcoma, and borderline vascular tumors (hemangioendothelioma). She and her co-workers are also credited with the first description of numerous new entities including: epithelioid hemangioendothelioma, spindle cell hemangioma (formerly spindle cell hemangioendothelioma), giant cell fibroblastoma, ossifying fibromyxoid tumor, epithelioid sarcoma-like hemangioendothelioma, pleomorphic hyalinizing angiectatic tumor, ischemic fasciitis, and inflammatory myxohyaline tumor (myxoinflammatory fibroblastic sarcoma), She has given generously of her time in many key leadership positions including Chair of the World Health Organization Committee for the Classification of Soft Tissue Tumors, President of International Society of Bone and Soft Tissue Tumors and President of the American Board of Pathology. Her honors include: Phi Beta Kappa, Alpha Omega Alpha, Alumnae Achievement Award (Wellesley College), the Society of Scholars (Johns Hopkins University) and 2014 Harvey Goldman Master Teacher and Mentoring Award (USCAP).