Lupus erythematosus (LE) is an autoimmune disease characterized by a heterogeneous spectrum of skin manifestations and organ affection, and is frequently associated with serum autoantibodies, which mostly remain positive through the course of the disease. The classification of LE is still a controversial topic.

To examine the prevalence and long‐term course of autoantibodies in patients with cutaneous LE (CLE) and/or systemic LE (SLE) treated in the outpatient clinic for connective tissue diseases of the department of Dermatology in Bochum, Germany.

Four hundred and two patients with LE were evaluated for antinuclear antibodies at a whole of 1572 time points. The prevalence as well as the long‐term positivity of antinuclear antibodies and their correlation with the various subtypes of disease was examined.

Antinuclear antibody (ANA) testing and anti‐ds‐DNA antibodies were not only more prevalent in SLE patients (as expected from the ACR criteria for diagnosis of SLE, P < 0.0001), but also have had a more consistent course in the long‐term evaluation (P = 0.0001 and P = 0.0111 respectively). Subacute cutaneous LE (SCLE) was associated with ANA (P = 0.0075), anti‐Ro (P < 0.0001) and anti‐La (P < 0.0001) antibodies, showing also higher consistency rates for these antibodies than discoid LE (DLE, P = 0.049, P = 0.004, P = 0.0004). Our data from 100 patients with LE tumidus (LET) support its perception as a distinct subtype of LE, not correlating with systemic disease or antinuclear antibodies (P < 0.0001). Anti‐U1‐ribonucleoprotein antibodies correlated with CLE in SLE patients (P = 0.0237), whereas non‐LE‐specific antinuclear antibodies were a rare, inconsistent autoimmune epiphenomenon in patients with SLE.

Long‐term analysis of antinuclear antibodies has shown significant differences in various clinical subtypes of LE, confirming the actual classification of the disease. A serial evaluation of antinuclear antibodies may support the classification of disease in LE patients with overlapping clinical features.