Changes in pigmentation has been reported for differing chemotherapeutic agents, such as cyclophosphamide, anthracyclines as well as hydroxyurea. Generalized hyperpigmentation as well as melanonychia has been well reported for hydroxyurea, which is neither dose dependent or related to the duration of treatment. It has never been report a case of hyperpigmentation of the tongue associated with the use of hydroxyurea, although it has been reported with other chemotherapeutic agents. We report a case of hyperpigmentation of the tongue associated with the use of hydroxyurea, discuss the differential diagnosis and a review the literature.