In the United States, there is currently no system to track donated human tissue products to individual recipients. This posed a challenge during an investigation of a nationwide tuberculosis outbreak that occurred when bone allograft contaminated with Mycobacterium tuberculosis (Lot A) was implanted into 113 patients in 18 U.S. states, including two patients at one healthcare facility in Colorado. A third patient at the same facility developed spinal tuberculosis with an isolate genetically identical to the Lot A outbreak strain. However, healthcare records indicated this patient had received bone allograft from a different donor (Lot B). We investigated the source of this newly identified infection, including the possibilities of Lot B donor infection, product switch or contamination during manufacturing, product switch at the healthcare facility, person-to-person transmission, and laboratory error. Findings included gaps in tissue traceability at the healthcare facility, creating the possibility for a product switch at the point-of-care despite detailed tissue-tracking policies. Nationally, 6 (3.9%) of 155 Lot B units could not be traced to final disposition. This investigation highlights the critical need to improve tissue-tracking systems to ensure unbroken traceability, facilitating investigations of recipient adverse events and enabling timely public health responses to prevent morbidity and mortality.