Background: There is limited evidence on the perception of medical marijuana (MM) among cancer patients in a legalized vs. a non-legalized state. In this study, we compared the attitudes of cancer patients in a legalized (Arizona) vs. a non-legalized state (Texas) on legalizing marijuana for medical use and their perception of its medical usefulness. We also examined their preference of MM for pain, anxiety and depression against current treatments and examined any demographic, physical or psychosocial association with its perception. Methods: Two hundred adult cancer patients were enrolled from the outpatient palliative care centers at Banner MD Anderson Cancer Center in Gilbert, AZ and The University of Texas MD Anderson Cancer Center in Houston, TX. All patients were residents of the state where they were enrolled. Various physical and psychosocial instruments were collected including a survey designed to determine attitudes and beliefs of patient towards MM. Due to the sensitivity of information, no identifiers were associated with data recorded. Results: No significant difference was found between both locations in attitude towards legalizing MM [Arizona 92% (85 - 97%) vs. Texas 90% (82 - 95%); p = 0.81] and belief of its usefulness [Arizona 97% (92 - 99%) vs. Texas 93% (86 - 97%); p = 0.33]. Patients preferred MM over current treatments for anxiety [60% (51 – 68%); p = 0.003] but not for pain and depression. Patients who favored legalizing MM were younger (median age 59 vs. 67 y; p = 0.027) and had worse Edmonton Symptom Assessment System fatigue (median 5 vs 3; p = 0.015) and appetite (median 3 vs 0.5; p = 0.004) scores. There was a significant difference among those who have used MM (95%) and have not used MM (88%) in support of legalization of MM (p = 0.024). Conclusions: Cancer patients from both legalized and non-legalized states showed strong support for legalization of marijuana for medical purposes and strong belief in its medical use. Patient who are younger, and had worse fatigue and appetite showed higher support for medical marijuana.