Introduction: Patients with serious illness often have pain, uncontrolled symptoms, and poor quality of life. Evidence continues to evolve regarding the role of cannabis to treat chronic pain, nausea, and anorexia. Little is known about how patients with serious illness perceive its benefits and harms. Given that an increasing number of clinicians across the United States are treating patients with medical cannabis, it is important for providers to understand patient beliefs about this modality. We assessed patient perceptions of benefits and harms of cannabis who obtained a medical cannabis card within an ambulatory palliative care (APC) practice. Methods: We recruited patients with a medical cannabis card, allowing for legal possession of cannabis oil, from an APC practice in Georgia. All participants reported using cannabis products. Patients completed an online survey that included questions about their cannabis use, concurrent opiate or controlled medication use, and perceptions of benefits and harms of cannabis. Results: All 101 patients invited to participate completed the survey. A majority had cancer (76%) and were married (61%), disabled or retired (75%), older than 50 years of age (64%), and men (56%). Most patients ingested (61%) or vaporized (49%) cannabis products. A majority of respondents perceived cannabis to be important for their pain (96%) management. They reported that side effects were minimally bothersome, and drowsiness was the most commonly reported bothersome harm (28%). A minority of patients reported cannabis withdrawal symptoms (19%) and concerns for dependency (14%). The majority of patients were using concurrent prescription opioids (65%). Furthermore, a majority of cancer patients reported cannabis as being important for cancer cure (59%). Conclusion: Patients living with serious illnesses who use cannabis in the context of a multidisciplinary APC practice use cannabis for curative intent and for pain and symptom control. Patients reported improved pain, other symptoms, and a sense of well-being with few reported harms.