Methadone is a very effective second-line opioid for treatment of cancer pain. However, the starting doses of methadone indicated on opioid conversion charts may over-estimate the dose of intravenous (i.v.) methadone needed. In this report, we describe four patients with cancer-related pain treated with continuous i.v. morphine and hydromorphone. Because of persistent pain and opioid side effects limiting increases in opioid dose, each patient was switched to i.v. methadone. All four patients had excellent pain relief without significant side effects at a dose that, according to the available conversion charts, was approximately 3% of the calculated equianalgesic dose of hydromorphone. When converting from continuous i.v. hydromorphone to continuous i.v. methadone, much lower doses than those suggested by the opioid conversion charts should be used as starting doses.