Existential distress has been recognized as a source of suffering for oncology patients. This study focusses on existential issues and coping mechanisms of a unique culturally diverse Jewish/Middle Eastern oncology population. A qualitative assessment of 40 patients with advanced cancer was undertaken through an interview process addressing the following themes: autonomy, dignity/body image, social isolation, coping mechanisms, guilt/past disappointments, spiritual health, meaning, hope and death/dying. The findings of this study indicate that existential concerns are endemic in this patient population, but that significant distress is relatively uncommon. Early palliative measures, family support, effective coping strategies, and religious belief systems may influence the way patients with advanced cancer deal with existential concerns.