We report the cutaneous side effects of Iressa (ZD1839), a new anti-cancer agent that acts by inhibiting epidermal growth factor receptor signal transduction. The most common cutaneous adverse effect was the development of an acneiform eruption on the face, anterior trunk and back (39%). The second most common side effect was xerosis or desquamation of the face, body or distal parts of the fingers or toes (36%). Additional cutaneous side effects included multiple ingrown paronychial inflammation of the toes and fingers (6%), small ulcers of the oral mucosa or nasal mucosa, and urticaria. The cutaneous adverse effects of Iressa are similar to those of other epidermal growth factor receptor-targeted agents and result from direct interference with the functions of epidermal growth factor receptor signalling in the skin. Iressa-induced acne may be related to excessive follicular hyperkeratosis, follicular plugging, obstructions of the follicular ostium and alteration of hair cycle progression, which lead to an inflammatory response. Xerosis or desquamation reflects a disturbance of the equilibrium between proliferation and differentiation of epidermis. The mechanism by which Iressa leads to the development of paronychia and ingrown nail remains unclear.