Although existential needs are highly prevalent in patients with cancer, specific sources of meaning have been little explored. We investigated whether specific sources of meaning predict global meaning and psychological distress. N = 258 patients with breast (45%), lung (39%) and gynaecological cancer (16%) completed a battery of validated questionnaires at T1. Six months later (T2), n = 183 (78%) patients participated again. The primary outcomes – sources of meaning, global meaning and psychosocial distress – were measured with the Sources of Meaning Profile-Revised (SOMP-R), Life Attitude Profile-Revised (LAP-R) and modules for depression and anxiety of the Patient Health Questionnaire (PHQ-9, GAD-7). Most important sources of meaning were ‘engaging in personal relationships’, ‘preserving human values and ideals’ and ‘feeling financially secure’. Stepwise multivariate regression analyses controlling for demographic and medical factors revealed that ‘engaging in personal relationships’, ‘preservation of culture and tradition’ and ‘interest in social and/or political causes’ predicted lower depression. ‘Leaving a legacy for the next generation’ and ‘feeling financially secure’ predicted both higher depression and anxiety. The findings highlight the relevance of sources of meaning for the psychological well-being of cancer patients and point towards specific sources of meaning that should be focused in psychosocial interventions.