This study was conducted to investigate the presence and characteristics of the ultrasound lesions that may be found in the entheses of patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. This cross-sectional study included 15 patients with SAPHO syndrome and 30 healthy controls matched for age, sex and body mass index. Subjects with regular sport activities as well as those with other rheumatic conditions were excluded from the study. Ultrasonography was used in both groups to study 14 entheses of the upper and lower extremities. Different elementary lesions representative of enthesis damage were defined. A total of 210 entheses in the study group and 420 in the control group were evaluated. Only one patient presented clinical enthesitis. In the study group, seven of the 15 patients (47%) showed morpho-structural entheseal alterations, versus only four of the 30 controls (13.3%; p < 0.001). The subjects with SAPHO showed ultrasound alterations in 32/210 entheses (15%), while the controls showed alterations in 20/420 entheses (4.8%), p < 0.001. The entheses with the largest number of morpho-structural alterations were those of the patellar and Achilles tendon. None of the controls showed power Doppler signal at enthesis or perienthesis level. Ultrasound evidence of enthesopathy seems to be a common feature in this series of patients with SAPHO syndrome.