The importance of self‐compassion in the context of medical problems has been highlighted in previous research. Its role in the psychological adjustment of cancer patients, however, has remained unexplored. The current study aimed at examining whether self‐compassion and self‐critical judgement would distinctively predict general psychopathological symptoms and quality of life in three distinct groups: a mixed sample of cancer patients (n = 63), patients with chronic illnesses (n = 68) and healthy subjects (n = 71). Correlation analyses revealed significant associations between lower self‐compassion and increased depressive and stress symptoms, and lower scores in quality of life dimensions in the patients' samples. The opposite correlational pattern was found regarding self‐critical judgement. In the case of healthy subjects, these correlations were weaker or nonsignificant. Regression analyses revealed that in patients with chronic illnesses, self‐critical judgement emerged as the best predictor of depressive and stress symptoms, and quality of life dimensions. In patients with cancer, however, it was the affiliate dimension of self‐compassion that was found to significantly predict lower levels of depressive and stress symptoms, and increased quality of life. These findings have important clinical implications by suggesting the relevance of nurturing a caring and kind relation with oneself in the face of challenging medical conditions, particularly in patients with cancer. Copyright © 2013 John Wiley & Sons, Ltd. Key Practitioner Message The link between self‐compassion and psychopathology and quality of life was examined in a mixed sample of cancer patients, in chronic patients, and in healthy subjects. Self‐compassion is associated with decreased psychopathological symptoms of stress and depression, and better quality of life in patients with chronic illnesses, and especially in patients with cancer. Psychological supportive interventions targeting the development of self‐compassionate attributes and skills may have beneficial effects in the psychological adjustment of medically ill patients, namely patients with cancer.