BACKGROUND Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent. The available therapeutic options provide only limited success or temporary benefit. METHODS A 20-year-old man presented with a 7-month history of recurrent episodes of swelling of the upper lip without pain, burning or local pruritus. No causative factors, such as food, drugs or latex, or physical, chemical or emotional conditions could be identified. The patient had been treated with oral antihistamines and corticosteroids with no clinical improvement. Physical examination showed firm edema without fovea, limited to the central area of the upper lip without epidermal changes or symptoms on palpation. The patient had a previous history of facial palsy 6 years previously and recurrent episodes of herpes simplex labialis. Skin prick tests with inhalant aeroallergens, food, latex and Anisakis allergens were negative. Laboratory investigation revealed normal complete blood count, erythrocyte sedimentation rate, thyroid hormones, biochemistry, complement components (C3, C4 and C1-esterase inhibitor) and CH50, rheumatoid factor, antinuclear antibodies, immune complexes, protein electrophoresis and immunoglobulins. Thorax and paranasal sinus radiographs were clear. Biopsy of the involved area of the lip showed edema with lymphocytic and plasma cell infiltration and mononuclear perivascular infiltrates without granulomas, suggesting initial granulomatous cheilitis. Because the patient showed lack of response and/or poor tolerance to prior treatments (deflazacort, clofazimine and metronidazole), intralesional triamcinolone injections were administered with satisfactory response from the first session. CONCLUSIONS Response to available treatments for Melkersson-Rosenthal syndrome is highly variable. In the present case, intralesional triamcinolone injections were effective.