Positive antinuclear antibodies are important in the diagnosis, disease determination, and efficacy evaluation of autoimmune diseases, especially for diagnosis with high sensitivity, and are widely used in the initial screening of autoimmune diseases. First, strictly speaking, antinuclear antibodies are not a single antibody, but a group of autoantibodies with different clinical significance, which can also be referred to as antinuclear antibody spectrum, such as anti-double-stranded DNA antibody, anti-Sm antibody, anti-histone antibody, anti-synuclein antibody, anti-SSA antibody, anti-SSB antibody, etc. Secondly, the clinical significance of different types of antinuclear antibodies varies, such as anti-double-stranded DNA antibody and anti-Sm antibody are specific for SLE; anti-SSA antibody and anti-SSB antibody are mostly seen in dry syndrome; anti-Scl-70 antibody is mostly seen in systemic sclerosis; anti-Jo-1 antibody is seen in myositis, etc. Thirdly, the positive rate and specificity of different types of antinuclear antibodies in related diseases differ greatly. For example, anti-double-stranded DNA antibodies and anti-Sm antibodies are both specific for SLE, but the positive rate of the former can reach 60%-90%, while the positive rate of the latter is only about 20%. In addition, pharmacologic factors and infections can lead to positive antinuclear antibodies. Therefore, the most common cause of antinuclear antibody positivity is autoimmune disease, but a definitive diagnosis needs to be made in conjunction with specific symptoms and signs. Patients with positive antinuclear antibodies should visit a rheumatologist as soon as possible for a comprehensive analysis to find the cause.