Usually acute leukemia in children presents with constitutional symptoms and abnormalities in blood investigations. But in certain proportion of cases leukemia can mimic certain orthopedic diseases like septic arthritis, osteomyelitis, juvenile rheumatoid arthritis and transient synovitis. Since the musculoskeletal manifestations are not pathognomonic, it will result in a delay in diagnosis and initiating treatment. The purpose of this review is to highlight the importance of considering acute leukemia as a differential diagnosis in children presenting with atypical and persistent musculoskeletal symptoms and signs.