A 47-year-old male developed both longitudinal melanonychia and periungual hyperpigmentation 6 months after initiation of hydroxycarbamide (synonym: hydroxyurea) therapy for chronic myeloproliferative disease. Based on the clinical symptoms observed in this patient, the broad differential diagnostic spectrum of hyperpigmentation of the nails is briefly reviewed here. In individuals who undergo hydroxycarbamide treatment, melanonychia might sometimes be seen as side effect and always has to be differentiated from subungual malignant melanoma.