Background: Oncology patients frequently have poor symptom control, particularly for pain and nausea. The use of medical marijuana (MMJ) has become more accepted, despite overall scant evidence of efficacy. As the majority of states have legalized MMJ, it is important for oncology providers to be able to counsel families regarding the role of MMJ. We examined the perceptions of adolescent and young adult (AYA) oncology patients and caregivers regarding MMJ to help providers frame their discussions. Methods: Questionnaires assessing history of recreational drug use, opinions regarding the role of MMJ in symptom management, perceived benefits, and side effects of MMJ were administered to AYA oncology patients and caregivers at three time points during treatment. Results: Twenty-four patients and 26 caregivers were enrolled. The majority of the patients and caregivers felt that MMJ should be discussed. Prior to treatment, caregivers perceived MMJ to have greater benefits than patients did. Knowing someone with substance abuse made patients and caregivers more likely to believe that MMJ would increase the risk of substance abuse and to perceive worse side effects from MMJ. Although not statistically significant, caregivers who had previously used marijuana tended to be more willing for their children to try MMJ for symptom relief than caregivers with no history of use. Conclusions: Understanding families’ prior experiences with substance abuse is important when counseling them regarding MMJ during the patient’s treatment. In general, families reported that MMJ should be discussed, but this can be influenced by the families’ prior experience.