Objectives More self-compassion has been related to a better psychological functioning in cancer patients, but little is known about the course of self-compassion over time in the trajectory of illness and cancer treatment. This longitudinal study aimed to examine subgroups of cancer patients with differential trajectories of self-compassion and associations of these trajectories with the course of psychological symptoms. Methods A total of 153 cancer patients participated in this longitudinal study. Self-reported questionnaires were used to measure self-compassion (i.e., overall self-compassion and, separately, positive self-compassion, and negative self-compassion), and depressive and anxiety symptoms. These assessments were taken directly after cancer diagnosis (T1), and at the start (T2) and the end (T3) of medical treatment. Latent class growth modelling and repeated measures ANOVA were applied to examine the research questions. Results We identified three trajectories of overall self-compassion ("stable low" 82.2%, "late increase" 11.8%, and "late decrease" 6.0%), four trajectories of positive self-compassion ("late decline" 57.2%, "early decline" 22.4%, "large increase" 15.1%, and "large decline" 5.3%), and four trajectories of negative self-compassion ("late decline" 42.1%, "stable negative self-compassion" 40.8%, "large fluctuation" 9.9%, and "large increase" 7.2%). Only the negative self-compassion trajectories were significantly related to the course of depressive and anxiety symptoms. Conclusions Our findings suggest that subgroups of cancer patients exist that show distinct trajectories of self-compassion over time. We identified a small group of patients at a higher risk of losing self-compassion throughout the cancer trajectory and experiencing psychological symptoms.