Patient-specific instrumentation (PSI) is a relatively new technology aimed at increasing the accuracy and efficiency of total knee arthroplasty (TKA). Its premise is reliant upon preoperative imaging techniques to acquire detailed measurements of a patient's distal femur and proximal tibia. Although a limited number of studies in the current literature have begun to critically evaluate this promising technology, a number of potential controversies exist. We present 2 patients with radiographic evidence of musculoskeletal neoplasms present on initial preoperative imaging that were not recognized prior to placement of patient-specific total knees. The expanding role of non-diagnostic imaging in TKA is examined, and we suggest guidelines for prevention of further devastating outcomes.