This prospective, controlled study was designed to assess the effectiveness of a preventive oral protocol in children receiving antineoplastic treatment for acute lymphoblastic leukemia (ALL). During a 13-month period, 96 children from one to 16 years of age with a diagnosis of ALL were evaluated. When the study was initiated, 60 patients already undergoing chemotherapy received palliative treatment for complications (Group I). Thirty-six children (Group II) with newly diagnosed ALL received a daily preventive protocol consisting of: (1) elimination of bacterial plaque; (2) application of a mouthwash with a non-alcoholic solution of chlorhexidine 0.12% and (3) topical application of lodopovidone, followed by “swish and swallow” with nystatin 500,000 units. Children in both groups were examined every 7 to 14 days by our pediatric dentistry team. We found a significant improvement in oral hygiene (p = 0.001) and a significant decrease in the incidence of mucositis grade 2 (p = 0.0013) and oral candidiasis (p = 0.009) in the Group II children. These findings show that the systematic application of a preventive protocol significantly reduces the incidence of oral complications. The results of this study identify a need to include a pediatric dentist in a multidisciplinary team which provides oral care for cancer patients.