Painful disorders of the patellofemoral joint are one of the most frequent complaints in orthopaedic and sports medicine. The purpose of this study was to assess the value of single photon emission computed tomography (SPECT) bone imaging compared with arthroscopy in the differential diagnosis of anterior knee pain. Twenty-seven patients with chronic anterior knee pain and 27 age matched control patients were examined prospectively. All patients underwent a detailed clinical history and a thorough physical examination of the knee. Planar and SPECT knee scintigraphy was performed using 99mTc methylene diphosphonate (99mTc-MDP). Subsequently, arthroscopic examination of all three compartments of the affected knee was performed. The association between the scintigraphic findings and arthroscopy was examined statistically. Planar and SPECT scintigrams were classified as follows: focal or diffuse uptake in the patella only (eight patients), uptake in the patella and a corresponding focus in the distal femur (12 patients), and uptake in the patella associated with linear increased activity along the distal femur (six patients). One patient had no patellofemoral SPECT abnormalities. Six of eight patients with isolated increased patellar activity were diagnosed with chondromalacia of the patella, while 2/8 patients had arthroscopic findings unrelated to patellofemoral abnormalities. Seven of 12 patients with corresponding uptake in the patella and distal femur were diagnosed with patellofemoral arthritis. Eleven other patients with corresponding patellar and femoral activity were diagnosed with increased lateral patellar compression syndrome. In these patients the patellar foci were always lateral, and they separated during flexion of the knee. Seven patients had further scintigraphic findings in addition to patellofemoral abnormalities, unsuspected clinically. Nine of 27 patients in the control group (33%) had either focal or diffuse increased patellar uptake. Compared to arthroscopy SPECT imaging had a sensitivity of 100% for patellofemoral abnormalities and a specificity of 64% (negative predictive value, 100%; and positive predictive value, 72%). The overall observed agreement between SPECT and arthroscopy was 81% (κ = 0.63). It is concluded that SPECT imaging of the knee is highly sensitive for the diagnosis of patellofemoral abnormalities. SPECT significantly improves the detection of maltracking of the patella and the ensuing increased lateral patellar compression syndrome. This information could be used to treat patellofemoral problems more effectively.