Background: Monitoring of kidney essential during the course of chemotherapy. Serum creatinine is of limited value in early detection of renal insufficiency. Cystatin C has proved to be a good marker for detection of early reduction in glomerular filtration rate (GFR). Objectives: To assess serum cystatin  C in children receiving chemotherapy and to compare its sensitivity with serum creatinine in detecting early reductions in GFR. Methods: Serum cystatin C (Cc.), serum creatinine (Cr.) and corrected creatinine clearance (c.Cr.cl) levels were assessed in 34 children with different types of malignancy just before the start of chemotherapy and again in 33 of them one month later. Patients were compared to 14 healthy controls of matched age and sex. Results: Before the start of chemotherapy, all patients when compared to controls had normal Cc [median (IQR) = 0.57 (0.4-0.7) vs 0.4 (0.32-0.66) mg/L, P = 0.1], Cr. [median (IQR) = 0.7 (0.6-0.8) vs 0.7 (0.57-0.8) mg/dl, P = 0.62], and c.Cr.cl [median (IQR) = 115.35 (104.4-137.1) vs 115.8 (111.5-130.9) ml/min/1.73m², (P ˂ 0.001) and a significant decrease in their c.Cr.cl (P ˂ 0.001). On the other hand their serum Cr. Levels did not change significantly (p = 0.65).c.Cr.cl negatively correlated with both Cc and Cr (r = -0.622, p ˂ 0.001), (r = -0.346, p = 0.045) respectively before the start of chemotherapy and        also after chemotherapy (r = -0.577, p ˂ 0.001) and (r = -0.45, p = 0.009), repectively. When pretreatment levels of Cc and Cr were used predict patients who developed ˃ 20% reduction in GFR after therapy, only Cc was statistically significant (P = 0.03). A cut off point of 0.57 mg/L with sensitivity of 77.8%; specificity of 63%, and an overall accuracy of 74% was suggested. Conclusions: Children with malignant diseases develop significant reduction in their GFR during the induction phase of chemotherapy despite the fact that their serum creatinine level may not change significantly. Cystatin C as a more sensitive marker than creatinine in detecting mild reduction in GFR can be used to predict patients who will develop renal impairment during the induction phase of chemotherapy.