Introduction: that saliva, is a biofluid, that is totally non-invasive & readily available, has long-been recognized to address the second roadblock which makes it a perfect diagnostic tool especially for children including leukemia ones. The salivary diagnosis when accompanied cytopathological studies in leukemic children will truly allow the bridging of the oral health research into systemic diseases as cancer via the biofluid the fillers & processes itself from the vasculature that nourishes the salivary glands into the oral cavity.Materials and Methods: The study sample included the first group included 100 patients from out patient clinic of the National Cancer Institute, Pediatric department, Cairo University diagnosed for leukemia. The other group was 100 medically free patients selected from out patient clinic of the Pediatric Dentistry department, Faculty of Oral and Dental Medicine, Cairo University as a control group of the same age group 7-14 years.The study was performed through 6 months. Intraoral examination for both groups including oral mucositis, gingival enlargement, fungal infections and dental examination including DMF and def used for caries detection and plaque index for plaque assessment.Results: There was a significant difference between all cases (Denovo cases and cases treated with chemotherapy) and controls as regard dental examination (p<0.001) including DMF, def and PL index.During salivary analysis results showed a significantly higher percent of cocci among cases (50 percent) in comparison to controls (10%)(p<0.001) also revealed that candidal infections were significantly higher among cases than among controls (p<0.001).Conclusion: In this study 13% of Denovo cases their oral manifestations indicated early signs of leukemia and through cytopathological analysis and through saliva analysis this study found that early diagnosed children (Denovo) who are high risk to leukemia by the observing exacerbaction with presence of atypical cells where immunological study for theirmonoclonclity were done also indicating oral symptoms like oral ulcers withmucositis and glossitis and gingival enlargement with a gingival nodules were initial presentation and were initial signs for leukemia.