Anterior knee pain is commonly associated with patellofemoral malalignment. Both conventional radiographic measurements and CT measurements have been proposed to define and confirm the sometimes difficult clinical diagnosis of anterior knee pain secondary to patellofemoral malalignment. Using CT imaging with computerized technique to measure anatomic relationships, we evaluated patients (n = 50) with anterior knee pain for excessive lateralization of the tibial tubercle. The symptomatic knee of each patient was compared with their asymptomatic knee as well as with the knees of patients with other causes of anterior knee pain (n = 10) and with the knees of asymptomatic controls (n = 10). The symptomatic knee of patients with suspected patellofemoral malalignment demonstrated significantly greater lateralization of the tibial tubercle (12.2 +/- 0.5 mm) than did the asymptomatic knee (9.0 +/- 0.7 mm). The symptomatic knees of patients with patellofemoral malalignment also demonstrated significantly greater lateralization of the tibial tubercle than did the knees of patients with other causes of anterior knee pain (5.9 +/- 0.9 mm). When a control population was added to the analysis, the patients with symptomatic patellofemoral malalignment demonstrated significantly greater lateralization of the tibial tubercle than did the controls (6.4 +/- 0.4 mm). Using a critical value of 9 mm lateralization, the CT diagnosis of patellofemoral malalignment had a specificity of 95% and a sensitivity of 85%. We conclude that CT determination of tibial tubercle position assists the diagnosis of patellofemoral malalignment.