Major apthous stomatitis induced by nicorandil is exceptional, the mechanism is still unknown and the histological aspect of these lesions have not been previously reported. Our case reports a man who was treated by nicorandil for coronary artery disease. He was referred for major aphtous stomatitis; one element was biopsied. The histological aspect was an aspecific sialadenitis, with granulous reaction, and without vasculitis or eosinophilic infiltration. We conclude that aphtous stomatitis induced by nicorandil could to be explain by a toxic effect, rather than a toxicallergic or immunologic mechanism.