The use of supplemental doses of opioids is commonly suggested to manage breakthrough pain. A comparative study of intravenous morphine (IV-MO) and oral transmucosal fentanyl citrate (OTFC) given in doses proportional to the basal opioid regimen was performed in 25 cancer patients receiving stable opioid doses. For each episode, when it occurred and 15 and 30 min after the treatment, pain intensity and opioid-related symptoms were recorded. Fifty-three couples of breakthrough events, each treated with IV-MO and OTFC, were recorded. In episodes treated with IV-MO, pain intensity decreased from a mean of 6.9 to 3.3 and to 1.7 at T1 and T2, respectively. In episodes treated with OTFC, pain intensity decreased from a mean of 6.9 to 4.1 and to 2.4 at T1 and T2, respectively. Statistical differences between the two treatments were found at T1 (P=0.013), but not at T2 (P=0.059). Adverse effects were comparable and were not significantly related with the IV-MO and OTFC doses. Intravenous morphine and OTFC in doses proportional to the scheduled daily dose of opioids were both safe and effective, IV-MO having a shorter onset than OTFC. Future comparative studies with appropriate design should compare titration methods and proportional methods of OTFC dosing.