Infliximab has become increasingly important in the treatment of SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. There is, however, little experience with this biological agent, and treatment protocols usually follow the regimens for spondylarthropathies. We report a patient with a highly unusual and severe clinical presentation of SAPHO syndrome including widespread bone and skin disease, and collagenous colitis. Infliximab treatment (5 mg/kg) given at weeks 0, 2 and 6 and every 8 weeks thereafter, induced rapid remission of the osteoarticular symptoms, although the skin lesions improved only partially, and after 10 months continuous therapy with infliximab a bone scan even uncovered new active bone lesions. Collagenous colitis is unresponsive to tumour necrosis factor α (TNFα) blocking agents. This moderate response to infliximab may indicate that a more aggressive treatment protocol is mandatory. We further believe that remission of osteoarticular complaints should be routinely confirmed by scintigraphic findings to verify treatment response.