We report an unusual case of a 43-year old female patient suffering from multiple sclerosis, who was treated with mitoxantrone. Few weeks after treatment initiation a hyperpigmentation of the patient's left thumb and index was noted. Following dose-reduction (from 12 to 10 mg/m(2)) and over the further course of mitoxantrone treatment the discoloration slightly faded. Although mitoxantrone is known to cause hyperpigmentation of various tissues this is the first report of melanonychia without hyperpigmentation of other tissue. Albeit speculative, pathogenesis of selective melanonychia by mitoxantrone could involve selective activation of nail matrix melanocytes or endocrine disturbances involving melanocyte stimulating hormone.