Statement of Problem: Several studies have shown that herpes simplex infection is the most prevalence etiologic factor for oral ulcers in patients under chemotherapy, and in leukemia.Purpose: The aim of this study was to investigate the clinical characteristics of oral ulcers and their relation with herpes simplex virus infection in patients undergoing chemotherapy.Materials and method: This descriptive and cross- sectional study was performed on patients receiving chemotherapy in Kerman hospital in 2006. Forty one patients (31 males and 10 females) with oral ulcers were studied. The most common type of cancer was acute lymphocytic leukemia diagnosed in 20 patients. Samples were prepared from ulcers by sterile swabs and were sent to laboratory for Polymerase Chain Reaction (PCR) procedure. The obtained data were analyzed by chi- square and t- test using SPSS 13.5 program.Results: In this study, of all patients with oral ulcers, 75.6% were men and 24.4% were women. The result of PCR test was positive in 28 cases (68.3%). Thirty patients (73.2%) had single oral ulcer and 11 cases (26.8%) were suffered from multiple ulcers. The most prevalence sites for the oral ulcers were tongue, buccal mucosa, and lip.Conclusion: It was concluded that the etiologic factor of oral ulcers in more than 50% of the patients under chemotherapy was herpes virus infection. Therefore, the antivirus treatment with prophylaxis should be performed for these patients. In addition, it must be considered that the clinical symptoms in diagnosis of this infection are not sufficient, and other tests such as PCR should be used.Key words: Oral ulcer, Herpes simplex virus, Chemotherapy