The diagnosis of acute renal graft dysfunction is discussed, highlighting renal biopsy and mo­lecular testing as essential. Although classical biopsies are the gold standard, the importance of a thorough histological analysis, including electron microscopy, which can provide valuable diagnostic and prognostic data, is emphasized. The need to send adequate samples to the pa- thologist to improve the detection of rejection and the importance of a clinical-pathological correlation are highlighted. In addition, techniques such as immunohistochemistry to identify rejection components and viruses, as well as markers to evaluate the presence of immune cells, are described. In summary, the work advocates a multidisciplinary approach and the use of advanced techniques to adequately diagnose renal graft dysfunction.