This paper reports a 2-year experience of more than 5,000 cross-match tests for renal transplantation. Tests were performed by means of both standard light microscopy and an innovatory method based on flow cytometry, an up-to-date investigative technique for computerized analysis of individual cell characteristics. Flow cytometry allowed a better detection of weak positive reactions (false-negative cross-matches) than light microscopy, thus reducing the risk of selecting candidates with donor presensitization. Transplant clinical outcome supported the value of this original and advanced technological method.