The aim of this study was to ascertain whether knee SPET can localize lesion sites in patients with internal derangements of the knee. We performed knee SPET as a pre-arthroscopic examination in 63 consecutive patients. SPET imaging was performed with a triple-headed SPET camera 4 h after the injection of 99Tcm-methylene diphosphonate. Arthroscopic diagnoses were as follows: 28 medial meniscus injuries, 24 lateral meniscus injuries, 31 anterior cruciate ligament (ACL) injuries, three posterior cruciate ligament injuries and one medial collateral ligament injury. Of 30 patients with crescent-shaped increased activity at the medial tibial plateau, 22 had medial meniscus injuries (positive predictive value: PPV 73%); of 17 patients with crescent-shaped activity at the lateral tibial plateau, 13 had lateral meniscus injuries (PPV 76%). Of 18 patients with increased activity at ACL attachment sites (primary sign), 17 had ACL injuries (PPV 94%). Of 27 patients with increased activity at bone impaction sites of ACL injury (secondary sign), 22 had ACL injuries (PPV 81%). Of 32 patients who had either a primary or secondary sign, 26 had ACL injuries (PPV 81%). We conclude that knee SPET is very useful in the management of internal derangements of the knee, particularly in determining the need for arthroscopy by localizing lesion sites.