By eliminating the requirement for participants to make frequent visits to research sites, mobile phone applications (“apps”) may help to decentralize clinical trials. Apps may also be an effective mechanism for capturing patient-reported outcomes and other endpoints, helping to optimize patient care during and outside of clinical trials. We report on the usability of Digital BioMarkers for Clinical Impact (DigiBioMarC™ (DBM)), a novel smartphone-based app used by cancer patients in conjunction with a wearable device (Apple Watch®). DBM is designed to collect patient-reported outcomes and record physical functions. In a fully decentralized “bring-your-own-device” smartphone study, we enrolled 54 cancer patient and caregiver dyads from Kaiser Permanente Northern California (KPNC) from October 2020 through March 2021. Patients used the app for at least 28 days, completed weekly questionnaires about their symptoms, physical functions, and mood, and performed timed physical tasks. Usability was determined through a subset of the Mobile App Rating Scale (MARS), the full System Usability Scale (SUS), the Net Promoter Score (NPS), and semi-structured interviews. We obtained usability survey data from 50 of 54 patients. Median responses to the selected MARS questions and the mean SUS scores indicated above average usability. The NPS from the semi-structured interviews at the end of the study was 24, indicating a favorable score. Cancer patients reported above average usability for the DBM app. Qualitative analyses indicated that the app was easy to use and helpful. Future work will emphasize implementing further patient recommendations and evaluating the app’s clinical efficacy in multiple settings.