BACKGROUND : Transdermal therapeutic system fentanyl with a drug release rate of 12 microg/h should be of special value in pediatric cancer pain control. Such a fentanyl formulation allows for a stepwise dose increase, similar to that reported for sustained-release morphine. PATIENTS AND METHODS : Sixty-four male and female pediatric patients with moderate to severe chronic cancer pain, ages ranging 2-14 years, were included. Patients did not receive opioids prior to enrollment. Patients were observed for pain relief using the Visual Analog Scale and the Wong-Baker FACES Pain Rating Scale, play performance score, and for side effects. RESULTS : There was significant improvement of visual analog scale and FACES pain scores from the baseline to the second day of application (P < 0.001). By the 15th day, scores reached 1.18 +/- 0.393 and 1.13 +/- 0.35, respectively (P < 0.001). Play performance scale improved from the third day of application of the patch when compared with the baseline (P < 0.001), reaching 55.02 +/- 8.35 (P < 0.001) at the end of the study. The sedation score increased on the second day to 2 in 10 patients and to 3 in 54 patients. By the seventh day, 56 patients had a sedation score of 1. All patients returned to baseline by the 15th day. Itching was reported in 16 cases, and erythema occurred in 10 cases. No significant side effects were reported. CONCLUSION : Transdermal fentanyl was found to be an effective, safe, and well-tolerated treatment for pediatric cancer-related pain in opioid-naive patients with chronic moderate to severe pain. In this study population, evaluation of vital signs and physical examination did not suggest any safety concerns while using transdermal fentanyl.