Background: Information about the frequency of cannabinoid use and the clinical characteristics of its users in oncology supportive care is limited. This study explored associations between cannabinoid use and cancer-related clinical characteristics in a cancer population. Patients and Methods: This retrospective review included 332 patients who had a urine drug test (UDT) for tetrahydrocannabinol (THC) together with completion of an Edmonton Symptom Assessment Scale (ESAS) and cannabinoid history questionnaire on the same day that urine was obtained during 1 year in the supportive care clinic. Results: The frequency of positive results for THC in a UDT was 22.9% (n=76). Significant statistical differences were seen between THC-positive and THC-negative patients for age (median of 52 [lower quartile, 44; upper quartile, 56] vs 58 [48; 67] years; P<.001), male sex (53.9% vs 39.5%; P=.034), and past or current cannabinoid use (65.8% vs 26.2%; P<.001). Statistical significance was observed in ESAS items between the THC-positive and THC-negative groups for pain (7 [lower quartile, 5; upper quartile; 8] vs 5 [3; 7]; P=.001), nausea (1 [0; 3] vs 0 [0; 3]; P=.049), appetite (4 [2; 7] vs 3 [0; 5.75]; P=.015), overall well-being (5.5 [4; 7] vs 5 [3; 6]; P=.002), spiritual well-being (5 [2; 6] vs 3 [1; 3]; P=.015), insomnia (7 [5; 9] vs 4 [2; 7]; P<.001), and total ESAS (52 [34; 66] vs 44 [29; 54]; P=.001). Among patients who reported current or past cannabinoid use, THC-positive patients had higher total scores and scores for pain, appetite, overall well-being, spiritual well-being, and insomnia than THC-negative patients. Conclusions: Patients with cancer receiving outpatient supportive care who had positive UDT results for THC had higher symptom severity scores for pain, nausea, appetite, overall and spiritual well-being, and insomnia compared with their THC-negative counterparts. These results highlight potential opportunities to improve palliative care.