Objective The aim of the study was (1) to evaluate contrast enhancement patterns of subchondral cysts on magnetic resonance imaging and (2) to discuss possible radiological explanations of cyst enhancement based on existing theories of subchondral cyst formation in osteoarthritis. Materials and methods The Multicenter Osteoarthritis Study (MOST) is a NIH-funded longitudinal observational study for individuals who have or are at high risk for knee osteoarthritis. All subjects with available non-enhanced and contrast-enhanced MRI were included. The tibiofemoral and patellofemoral joints were divided in 14 subregions. The presence and size of subchondral cysts and bone marrow edema-like lesions (BMLs) were scored semiquantitatively in each subregion on non-contrast-enhanced MRI from 0 to 3. Enhancement of subchondral cysts was evaluated on contrast-enhanced MRI as grade 0 (absent), grade 1 (partial enhancement), or grade 2 (full enhancement). The adjacent articular cartilage was scored in each subregion on non-enhanced MRI as grade 0 (intact), grade 1 (partial thickness loss), or grade 2 (full thickness loss). Results Four hundred knees were included (1 knee per person, 5600 subregions). Subchondral cysts were detected in 260 subregions (4.6%). After intravenous contrast administration, 245 cysts (94.2%) showed full enhancement, 12 (4.6%) showed partial enhancement and 3 (1.2%) showed no enhancement. Enhancing BMLs were found in 237 (91.2%) subregions containing cysts, which were located adjacent or in the middle of BMLs. In 121 subregions (46.5%) having cysts, no adjacent full thickness cartilage loss was detected. Conclusion Most subchondral cysts demonstrated full or partial contrast enhancement, and were located adjacent or in the midst of enhancing BMLs. As pure cystic lesions are not expected to enhance on MRI, the term “subchondral cyst-like bone marrow lesion” might be appropriate to describe these lesions.