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Introduction. Psoriasis is a chronic inflammatory disease affecting approximately 2% of the population. Biologic agents are the new treatment options for patients with moderate to severe plaque psoriasis who have failed traditional systemic therapies. The therapy with tumor necrosis factor antagonists significantly increases the risk of reactivation of latent tuberculosis; therefore, screening is important before the introduction of biological treatment. Objective. Presentation of diagnostic difficulties in establishing an etiological factor of recurrent erythema nodosum in a 46-year-old woman treated with anti-TNF-α agents (etanercept and adalimumab) for plaque psoriasis and psoriatic arthritis. Case report. We present a case of a 46-year-old woman, treated with etanercept and adalimumab for plaque psoriasis and psoriatic arthritis. Despite prophylactic antituberculosis treatment before introduction of biological therapy, the patient developed erythema nodosum most likely caused by lymph node tuberculosis. Conclusions . The development of erythema nodosum, especially the recurrent form, in a patient with a positive tuberculin skin test and negative IGRA test treated with anti-TNF should always prompt increased vigilance and exclusion of active tuberculosis, which may develop even in patients who have undergone prophylactic antituberculosis treatment.