PURPOSE: Comparison of two safe complementary medicine methods to treat cancer-related pain and fatigue in adult patients with acute leukemia during active treatment with chemotherapy. METHODS: A randomized trial with three groups (light massage, music therapy, and standard care) in Ahvaz, Iran, between 2018 and 2019. A total of 104 participants of the massage and music therapy groups received 15-minute intervention sessions, thrice weekly for 4 weeks, and participants of the control group received standard care. Cancer-related pain and fatigue intensity were measured by numeric self-report rating scales. During the 4 weeks of the interventions, pain and fatigue intensity were measured weekly. All the groups were followed up for 2 weeks after the end of the intervention. RESULTS: Pain and fatigue intensity decreased significantly over time between the intervention groups compared with the standard care group. In the massage and music therapy groups, a progressive reduction of pain and fatigue intensity over time (from the baseline to the fourth week) was observed. Fatigue intensity did not differ between the two intervention groups. Pain intensity decreased more in the massage group compared with the music therapy group. The durable effects of the massage therapy were greater compared with the music therapy 2 weeks after the intervention was completed. CONCLUSION: Light massage was more effective and persisted longer than the music therapy for controlling leukemia-related pain and fatigue in adult patients with acute leukemia.