Objective: Although the Dutch Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being 12 Item Scale (FACIT-Sp-12) has been used in several Dutch studies, no study has assessed the measurement properties of the translation. The aim of this study was to perform an item-reduction analysis, confirmatory factor analysis (CFA), test of reliability, and test of convergent validity. Methods: From the baseline data of a cohort study on experienced quality of care and quality of life (eQuiPe study), 400 advanced cancer patients without missing values on any of the variables were selected. In addition to demographic and religious/spiritual characteristics, study measures included the FACIT-Sp-12 and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30). Results: Item reduction analysis showed that Items 4 and 8 had low correlations to the total scale (0.75). CFA indicated a good fit for a three-factor structure with Meaning, Peace and Faith, and good Cronbach's α coefficients for the total as well as the subscales (0.71–0.86). The removal of Items 4, 8, and 12 further improved the goodness of fit and Cronbach's α coefficients. Convergent validity was adequate with the EORTC-QLQ-C30. Conclusion: Our analysis of the FACIT-Sp-12 revealed serious questions about three items and concerns about the Faith subscale. These problematic items deserve further attention so should be interpreted with care when using this scale. A future study could look into the items and test possible replacements.