A 72-year-old man treated with 3.5% imiquimod cream for scalp actinic keratoses developed the usual crusted and erosive reaction but developed bullae on the scalp, as well as the limbs and torso after several weeks into treatment. Biopsy confirmed bullous pemphigoid. He was treated with clobetasol ointment, prednisone and methotrexate, with eventual disease control. He had a severe disease course. Bullous pemphigoid is usually idiopathic, but can be induced by skin trauma, as well as by several medications; this is the first report of imiquimod as a trigger. Imiquimod is a toll-like receptor 7 agonist that induces cellular apoptosis and recruits pro-inflammatory cytokines including tumour necrosis factor-alpha and interferon-alpha, which have been implicated in autoimmunity. This case highlights an unusual but severe adverse effect from topical imiquimod.