OBJECTIVE In our context, existential plight refers to heightened concerns about life and death when people are diagnosed with cancer. Although the duration of existential plight has been proposed to be approximately 100 days, evidence from longitudinal studies raises questions about whether the impact of a diagnosis of advanced cancer may require a longer period of adjustment. The purpose of our study was to examine spiritual well-being (SpWB) and quality of life (QoL) as well as their interrelationship in 52 patients with advanced cancer after 100 days since the diagnosis at one and three months post-baseline. METHODS The study was designed as a secondary data analysis of a cluster randomized clinical trial involving patients with stage 3 or 4 cancer undergoing treatment. SpWB was measured using the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp-12); common factor analyses revealed a three-factor pattern on the FACIT-Sp-12. Quality of life was measured with the Functional Assessment of Cancer Therapy-General (FACT-G). We limited our sample to participants assigned to the control condition (n = 52). RESULTS SpWB and QoL remained stable between one and three months post-baseline, which were a median of 112 and 183 days after diagnosis, respectively. SpWB was found to be associated with QoL more strongly than physical and emotional well-being. Peace and Meaning each contributed unique variance to QoL, and their relative importance shifted over time. Faith was positively related to QoL initially. This association became insignificant at three months post-baseline. CONCLUSIONS This study underscores the significance of SpWB for people newly diagnosed with advanced cancer, and it highlights the dynamic pattern of Peace, Meaning, and Faith in association with QoL. Our results confirm that patients newly diagnosed with advanced cancer experience an existential crisis, improve and stabilize over time. Future studies with larger samples over a longer period of time are needed to verify these results.