Hydroxyurea (HU) is an antimetabolic agent commonly used in myeloproliferative 
disorders and hematological diseases as well as in severe psoriasis. Despite of 
usually be well tolerated, sometimes it can induce immunosuppression and 
mucocutaneous adverse effects associated with discomfort or pain. Nevertheless, 
oral mucosal adverse reactions are extremely uncommon and present as ulcers, 
tongue depapilation and dyschromia. Complete remission of adverse effects is 
usually observed after withdrawal of the medication. The aim of this paper is to 
report two patients with oral lesions related to HU treatment. T0 he patients 
were adequately managed by changing hydroxyurea with imatinib mesilate. Oral 
lesions are rare complications of long-term hydroxyurea treatment and may be an 
indication of stopping therapy and substitution with imatinib mesilate.