Erythema nodosum is a skin lesion most often located on the anterior surface of the lower extremities. It initially appears as rounded nodules with a vivid red or purplish colour. Erythema nodosum may often be a predictive sign of systemic infectious or autoimmune diseases. Group A streptococcal infections, virological infections (cytomegalovirus and Epstein–Barr virus) and sarcoidosis are the most common aetiological factors of erythema nodosum. Certain drugs also may be the cause, whereas erythema nodosum is often idiopathic in clinical practice. It is more common in women. Erythema nodosum rarely affects children, but with equal prevalence in both sexes. It is important to note that basic diagnostic process should be performed in all cases of erythema nodosum. The diagnosis involves laboratory tests (complete blood count with differential, C-reactive protein levels, presence of rheumatoid factor, hepatic enzyme level) and medical imaging (chest radiograph, abdominal and thyroid ultrasound). Depending on the suspected etiological factor, the diagnostic process should be extended to include other, additional laboratory investigations. Erythema nodosum is caused by type IV delayed hypersensitivity reaction to a wide variety of possible stimuli. Additionally, circulating immune complexes cause complement activation in patients with erythema nodosum. The histopathological picture of skin lesions shows septal panniculitis (inflammation of subcutaneous fat tissue) with associated Miescher’s radial granulomas – aggregates of small histiocytes arranged around a central cleft. The most important therapeutic approach in erythema nodosum is the treatment of underlying disorders, if identified. If this is not possible, less potent topical corticosteroids and heparinoid ointments are used.