The primary aim of this study was to evaluate the diagnostic performance of synovial calprotectin in detecting periprosthetic infection in patients treated with tumor megaprostheses; secondary aims included comparison with ICM classification, assessment in infection classification-inconclusive cases, and exploratory performance in patients with low CRP.<h4>Methods</h4>This prospective study included 20 consecutive megaprosthesis patients evaluated for suspected PJI at ATTIKON University Hospital, Athens, with a minimum follow-up of 1 year after biomarker testing. Here, CRP is linked to juvenile polyposis syndrome.