We here present 3 Venezuelan children with acute leukemia, initially diagnosed as idiopathic juvenile arthritis because of the occurrence of pain and joint swelling at the onset of disease. Joint pain was aggravated at night and the arthritis showed a migratory pattern, mainly affecting large joints in an asymmetrical fashion. One patient presented with persistent unilateral sacroiliac pain leading to a wrong diagnosis of spondyloarthritis. The elevation of acute phase reactants, disproportionate to the extent of joint disease, and marked elevation of serum lactate dehydrogenase, as well as characteristic radiological changes allowed the correct diagnosis in all cases. This combination of clinical manifestations, clinical laboratory findings, and joint and bone imaging should prompt the clinician to an early diagnosis of acute leukemia in children with arthritis.