Recently, the use of methadone in cancer patients has increased due to in vitro studies indicating that methadone is capable of inducing cell death. However, thus far there are no relevant clinical studies indicating that the use of methadone can prolong survival in cancer patients. Based on low-quality evidence, methadone is a drug that has similar analgesic benefits to morphine and has a role in the management of cancer pain in adults. Other opioids such as morphine, hydromorphone, and fentanyl are easier to manage but may be more expensive than methadone in many economies. Methadone is an opioid that is only approved for replacement therapy in Austria. Methadone can be used as a second- or third-line agent for severe cancer-related pain, but its use should be restricted to experts. Here we report a series of cases of patients who developed problems when using methadone as an antitumor treatment, with a brief review on the role of methadone as a pain medication and the current lack of value as an anti-tumor therapy. Methadone is not approved or recommended as an anticancer treatment in Austria or Germany. The Austrian Association for Hemato-oncology (OeGHO), the Austrian Association for the Management of Pain (ÖSG), and the Austrian Association for Palliative Care (OPG) do not recommend the use of methadone as an anticancer treatment. Thus, from a medical and ethical point of view, the use of methadone as an antitumor therapy is to be rejected, based on the views of various Austrian (OeGHO, ÖSG, OPG) and German specialists. Unqualified use of methadone by nonexperienced pain therapists is dangerous and must also be rejected.