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Patients who face a stressful situation related to cancer and loss of a limb have not been thoroughly studied form a psychological perspective, what limits the possibilities of targeted psychological assistance and social rehabilitation. In this regard, the aim of the research was to study the clinical and psychological status, strategies and personal resources for coping with the stress of the disease, as well as the main parameters of the quality of life (QoL) of patients who underwent lower limb amputation due to cancer (group 1, n = 24, men — 62.5%, average age 47.25 ± 3.17), in comparison with patients amputated due to other somatic diseases not accompanied by an actual vital threat (group 2, n = 15, men — 93.3%, average age 59.67 ± 2.27), as well as with normative psychodiagnostic data. Methods of clinical and psychological diagnostics were used, including “Ways of Coping Questionnaire”, “Big V Questionnaire”, “Purpose in Life Test”, EORTC “Quality of Life of Cancer Patients Questionnaire” (QLQ-C30). It was found that functional capability (p