It is unknown whether lesions of steroid-related osteonecrosis of the knee increase or decrease in size during the course of the disease after diagnosis. We sought to determine whether steroid-related osteonecrosis of the knee would have spontaneous changes in size, and if so, the factors affecting the change. We performed baseline and followup (minimum of 1 year) magnetic resonance imaging scans on 30 knees of 17 patients. We then used image registration techniques to match two sets of images. Lesion size change was evaluated on all contiguous pairs of matched magnetic resonance images. Fourteen Stage 1 (preradiographic stage) knees in seven patients showed spontaneous incomplete regression without subsequent collapse. These patients had early steroid-related lesions detected within 3 years after starting steroid treatment and all showed bilateral and multifocal involvement; lesion regression occurred regardless of location. The initial size and location of the lesions and discontinuing steroid administration did not seem to affect regression. Regression can occur in some patients with early steroid-related osteonecrosis of the knee, and the time between initiation of steroid treatment and its diagnosis might be the most significant predictive factor.