Aim: To determine the imaging characteristics of SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome and seronegative spondyloarthropathies (SpAs) on whole-spine magnetic resonance imaging (WS-MRI) and evaluate the role of WS-MRI in the diagnosis and differentiation of the two diseases., Materials and Methods: Twenty-eight patients with SAPHO and 44 with SpAs were included. All patients were symptomatic and clinically diagnosed with SAPHO or SpAs, and all underwent WS-MRI for comparison of imaging characteristics., Results: The mean age of the SAPHO patients was 48.7 ± 12.7 years, while that of the SpA patients was 34.7 ± 12.3 years (p<0.001). WS-MRI showed that the frequency of cervical, thoracic, and lumbar spine involvement was 53.6% versus 52.3%, 75% versus 88.6%, and 60.7% versus 63.6%, respectively (p=0.70, 0.13, and 0.80). The frequency of sacroiliac joint involvement was 7.1% and 100% (p<0.001). Continuous spinal involvement accounted for 50% versus 43.2%, 60.7% versus 84.1%, and 39.3% versus 40.9% in the cervical, thoracic, and lumbar vertebrae, respectively (p=0.03). WS-MRI showed that bone marrow oedema of spinal anterior corner was observed in 50% versus 75% (p=0.03). Vertebral body and posterior attachment involvement accounted for 85.7% versus 93.2% and 14.3% versus 34.1% (p=0.3, 0.06). The frequency of bone erosion in mobile spine was 75% and 36.4%, respectively (p=0.02). The frequency of intervertebral disc, endplate, anterior thoracic wall, and paraspinal soft-tissue swelling was 42.9% versus 18.2%, 53.6% versus 22.7%, 85.7% versus 42.2%, and 50% versus 11.4% (p=0.02, 0.00)., Conclusions: Factors differentiating the two groups at WS-MRI were bone marrow oedema of the spinal anterior corner, bone erosion, and swelling of the intervertebral disc, endplate, anterior thoracic wall, and paraspinal soft-tissue., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)