Objectives Mindfulness and self-compassion are related to psychological well-being and can be regarded as personal resources. It is, however, unclear whether these resources are always beneficial (direct effect) or only in stressful circumstances (buffer effect). We therefore examined whether mindfulness and self-compassion are equally or more strongly related to depressive symptoms and affect in cancer patients, compared to healthy controls. Methods Using a case-control design, 245 cancer patients were matched to 245 healthy controls (without chronic somatic comorbidities). Both groups filled out questionnaires concerning mindfulness (Five Facet Mindfulness Questionnaire), self-compassion (Self-Compassion Scale), depressive symptoms (Center for Epidemiologic Studies Depression Scale), and affect (Positive and Negative Affect Scale). Using correlation and regression analyses, we examined within both groups the associations for mindfulness (i.e., total score and five facets) and self-compassion (i.e., total score, two factors and six facets) with depressive symptoms and affect. Results Mindfulness and self-compassion were equally strongly related to depressive symptoms and affect in cancer patients versus healthy controls. Mindfulness facets Act with awareness and Non-judgment were strongly related to depressive symptoms, negative affect, and the negative self-compassion factor. In contrast, mindfulness facets Describe and Observe were strongly related to positive affect and the positive self-compassion factor. When distinguishing the six self-compassion facets, Isolation and Mindfulness were strongly related to depressive symptoms, Over-identification to negative affect, and Mindfulness to positive affect. Conclusions Results suggest that mindfulness and self-compassion are basic human personal resources associated with psychological functioning, regardless of the presence or absence of stressful life experiences.