Background We investigated the clinical value of treating pediatric multiple kidney stones with extensive distribution using flexible ureteroscopic lithotripsy (FUL) combined with micro-percutaneous nephrolithotomy (micro-PNL). Patients and methods In total, 21 pediatric patients with multiple renal calculi between May 2016 and June 2017 received FUL combined with micro-PNL. The group included 13 boys and eight girls; the patients' mean age was 3.8 years (range 1-8 years). The maximum stone diameter ranged from 1.0 to 1.5 cm. FUL was first performed in the lithotomy position to fragment stones that were located in the renal pelvis, and upper and mid-renal calyx. Patients were then moved to a prone position, and micro-PNL was performed to treat lower pole stones that could not be reached by the flexible ureteroscope during FUL. Percutaneous renal access to the lower calyx was achieved using a 4.8F "all-seeing needle" with ultrasound guidance, and stone fragmentation was performed with a 200-mu m holmium laser at different settings to disintegrate 1- to 2-mm fragments. Results All 21 pediatric patients with multiple kidney stones underwent combined FUL and micro-PNL. The stone free rate (SFR) was 85.7% (18/21). The mean surgical time was 45 min (range 30-70 min). The mean volume of irrigation fluid used was 480 mL (range 300-1200 mL). The mean surgical time for FUL and micro-PNL was 31 min and 14 min, respectively, and the mean volume of fluid used for FUL and microPNL was 360 mL and 120 mL, respectively. According to the modified Clavien classification, grade 1 and 2 postoperative complications occurred in five and one patients, respectively. The mean decrease in the level of hemoglobin was 0.4 g/dL (0-0.7 g/dL), and no patients required a transfusion. The average hospital stay was 3 days (range 2-5 days). Conclusion Combined FUL and micro-PNL is a safe, effective, and minimally invasive operation to remove multiple renal calculi with extensive distribution in children in selected cases.