BACKGROUND Current equianalgesic reference tables, based largely on single dose studies, give dose ratios of 1:1 to 4:1 for oral morphine to oral methadone, which possibly are inaccurate in patients with cancer pain who are exposed to multiple doses of these opioids. The purpose of this study was to determine the equianalgesic dose ratio between morphine and methadone in patients with cancer pain and to establish whether the dose ratio changes as a function of previous opioid dose. METHODS A retrospective analysis of consecutive rotations involving morphine and methadone using standard selection criteria identified a total of 20 evaluable rotations (14 from morphine to methadone and 6 from methadone to morphine). Opioid doses and pain intensity levels pre- and postrotation were analyzed. RESULTS Median dose ratios (lower-upper quartiles) for morphine to methadone and methadone to morphine rotations were 11.36 (range, 5.98-16.27) and 8.25 (range, 4.37-11.3), respectively (P = 0.23). Combining all 20 rotations, a unified median dose ratio of 11.2 (range, 5.06-13.24) was calculated. There was no significant difference in pain intensity levels pre- and postrotation as recorded on a visual analogue scale. Univariate correlational analysis of dose ratio and the level of daily morphine dose prior to rotation revealed a Spearman correlation coefficient of 0.86 (P = 0.0001). In patients receiving >1165 mg per day prior to methadone rotation, a median dose ratio of 16.84 (range, 12.25-87.95) was observed, which was approximately 3 times higher compared with a median dose ratio of 5.42 (range, 2.95-9.09) (P = 0.007) for the 50% of patients receiving lower morphine doses. CONCLUSIONS The results highlight the general underestimation of methadone potency and the consequent risk of potential life-threatening toxicity. The strongly positive correlation between dose ratio and previous morphine dose suggests the need for a highly individualized and cautious approach when rotating from morphine to methadone in patients with cancer pain.