The two most common entities among generally rare but under-diagnosed autoinflammatory bone disorders are chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Due to their similarities, many authors consider CRMO to be a subtype of SAPHO syndrome. The aim of this study was to compare clinical, laboratory, and imaging features and outcomes of patients with CRMO and SAPHO. The analysis of the data from 6 children with CRMO (four girls and two boys, age 3.5-14 years) and of 6 children (6 boys, age 13.5-17.5 years) with SAPHO syndrome was performed. The initiating symptoms in all patients with CRMO were bone pain with multifocal bone lesions. There were no skin manifestations. Five out of six patients achieved control with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, while one patient required disease-modifying antirheumatic drugs (DMARDs). The initiating symptom in five patients with SAPHO syndrome were severe acne, while in one patient acne occurred two years after the disease onset. Two patients typically developed inflamed sternoclavicular joints and sternum, while the others showed changes affecting other skeletal regions. Three patients achieved control with NSAIDs and corticosteroids, the others required DMARDs and TNFα inhibitors. In comparison with patients with CRMO, patients with SAPHO suffered more frequent and longer lasting exacerbations. In conclusion, CRMO and SAPHO syndrome have an array of common characteristics, but also a number of differences. Nevertheless, further investigation into the etiopathogenesis is required to establish a definite relationship between CRMO and SAPHO.