In patients with advanced cancer (ACP), total suffering results from the interdependent physical, psychological, existential and sociocultural dimensions of illness. Whereas medicine treated the physical symptoms, the social, psychological and existential dimensions of suffering are usually tackled by psychologists. However, very few in-deep clinical data address the existential aspects of total suffering amongst ACP. Based on clinical case studies, this presentations aims at (1) better understanding when and how existential psychotherapy may be appropriate to help relieving total suffering in ACP; and at (2) formulating clinical recommendations for practicing existential psychotherapy with ACP. Main source of data arise from in-deep analysis of 5 clinical and longitudinal case studies. Patients were referred to the psychologist by their treating physician. They completed from 5 to 30 sessions of existential psychotherapy to address the psychological and existential aspects of their suffering. They agreed their clinical data to be used for research purposes. For all therapy sessions, detailed clinical records on the content and therapeutic process were kept and transcribed. Codification, analysis and interpretation of material followed Jonathan Smith’s interpretative phenomenological analysis. Two patients out of five didn’t experience existential psychotherapy as being helpful. Those patients finally requested palliative sedation to relieve their total suffering. Analysis of all 5 cases revealed meaningful variations of the following themes: (1) meaning of death, (2) temporality, (3) corporeality, (4) relationship with self and (5) relationship with others. The qualitative variations on those themes shed light on ACP’s existential experience of suffering and precise the possible benefits of existential psychotherapy. Results are discussed in the current debate surrounding the use of palliative sedation for total suffering. Based on the results, we suggest clinical guidelines in assessing and treating the existential aspects of total suffering. The heuristic and clinical values, and the methodological limitations of our results are discussed.