Purpose: The aim of this case series was to compare magnetic resonance imaging (MRI) with cone beam computed tomography (CBCT) in the representation of periapical osteolyses. Based on the histological findings, the potential of MRI for further lesion characterisation was investigated. Materials and methods: Thirteen patients (average age: 41 ± 27 years) with a total of 15 periapical lesions (five molars, five premolars, and five front teeth) were examined. Lesion characterisation was based on the homogeneity/heterogeneity of the lesions, the signal intensity within the lesion compared to the surrounding tissue and differences in the signal intensities between different MRI contrast weightings. Results were compared with CBCT and histological findings. Results: Although all patients presented with dental restorations, such as fixed partial dentures and filling materials, all periapical lesions could be diagnosed with either imaging modality. Histologically, 13 cysts and two apical granuloma were confirmed. In CBCT, the similar appearance of all lesions did not allow any further characterisation. In MRI, radicular cysts and granuloma could be characterised by their appearance in the MRI images with different contrast weightings. The MRI-derived characterisations were consistent with the histological findings. Conclusions: The presented study shows that the application of multi-contrast MRI may lead to better characterisation of apical lesions, thus enabling an improved patient-specific selection of the optimal treatment option.