Smoking contributes to 1 in 3 cancer deaths. At the Stanford Cancer Center, tobacco cessation medication management and counseling are provided as a covered benefit. Patients charted as using tobacco are contacted by a tobacco treatment specialist and offered cessation services. As a novel addition, this study examined the acceptability of a virtual reality (VR) mindful exposure therapy app for quitting smoking called MindCotine. The objective of this study was to determine the feasibility and acceptability of offering 6 weeks of MindCotine treatment as a part of Stanford's Tobacco Treatment Services for patients seen for cancer care. As part of a single-group pilot study, the MindCotine VR program was offered to English- or Spanish-speaking patients interested in quitting smoking. Given the visual interface, epilepsy was a medical exclusion. Viewed from a smartphone with an attachable VR headset, MindCotine provides a digital environment with audiovisual content guiding mindfulness exercises (eg, breathing techniques, body awareness, and thought recognition), text-based coaching, and cognitive behavioral therapy-based self-reflections for quitting smoking. Interested patients providing informed consent were mailed a MindCotine headset and asked to use the app for 10+ minutes a day. At the end of 6 weeks, participants completed a feedback survey. Of the 357 patients reached by the tobacco treatment specialist, 62 (17.3%) were ineligible, 190 (53.2%) were not interested in tobacco treatment services, and 78 (21.8%) preferred other tobacco treatment services. Among the 105 eligible and interested in assistance with quitting, 27 (25.7%) were interested in MindCotine, of whom 20 completed the informed consent, 9 used the program, and 8 completed their end-of-treatment survey. Participants using MindCotine completed, on average, 13 (SD 20.2) program activities, 19 (SD 26) journal records, and 11 (SD 12.3) coaching engagements. Of the 9 participants who used MindCotine, 4 (44%) reported some dizziness with app use that resolved and 7 (78%) would recommend MindCotine to a friend. In total, 2 participants quit tobacco (22.2% reporting, 10% overall), 2 others reduced their smoking by 50% or more, and 2 quit for 24 hours and then relapsed. In a feasibility and acceptability pilot study of a novel VR tobacco treatment app offered to patients at a cancer center, 4 of 9 (44%) reporting and 4 of 20 (20%) overall substantially reduced or quit using tobacco after 6 weeks and most would recommend the app to others. Further testing on a larger sample is warranted. ClinicalTrials.gov NCT05220254; https://clinicaltrials.gov/study/NCT05220254.