Breakthrough pain has been recognized as a challenging pain phenomenon, in cancer. Oral transmucosal fentanyl citrate (OTFC) recently has been recommended as treatment, but OTFC is not widely available. Therefore, alternatives are needed. In two separate pilot studies, 58 patients were instructed to self-administer subcutaneous (SC) rescue opioids (hydromorphone (n = 43), morphine (n = 11), or sufentanil (n = 4), using a standard injection-pen for breakthrough pain. Patients were asked to rate the overall efficacy of SC rescue opioids on a 3-point scale (not noticeable, moderate, or good). The efficacy was rated as good in 49 patients (84%, 95% CI: 73-91%), moderate in 8 patients (14%), and not noticeable in 1 patient (2%). The median dose per injection was equianalgesic to 25 mg of SC morphine (range: 4-150 mg). Twenty-nine patients (50%) were treated until death (n = 26) or were on ongoing treatment (n = 3). Patients were treated,for a median of 6 weeks (1 day-41 months). (c) 2005 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.