Background: Spirituality and spiritual needs of cancer patients are frequently mentioned in the nursing literature, but the most significant defining characteristics of spiritual distress in the context of clinical reasoning and nursing diagnosis are rarely explored. Understanding of these is important for effective spiritual intervention. Objective: The aim of this study was to identify the prevalence and the defining characteristics of the nursing diagnosis "spiritual distress," as classified according to NANDA International, among women with breast cancer. Methods: This was a quantitative and cross-sectional study, comprising the third phase of a larger study investigating the clinical validation of spiritual distress in cancer patients undergoing chemotherapy. Fehring's clinical diagnostic validation model was used to identify the prevalence and the major defining characteristics of the diagnosis. A convenience sample was used, and data were collected by structured interview. Results: A total of 70 women participated; most were married (62.9%) and had a mean age of 54 years, and 55.7% reported having at least 1 person depending on them. The average length of time since the cancer diagnosis was 30.9 months. Twenty-seven participants were experiencing spiritual distress (38.6%). Eleven defining characteristics were classified as major. Conclusions: The prevalence of spiritual distress and the major defining characteristics give clinical evidence about the nurse's role in providing spiritual care. The results are useful for the improved use of the NANDA International diagnoses within this domain. Implications for Practice: The findings highlight the importance of assessing the defining characteristics of the diagnosis as an objective strategy to improve clinical reasoning related to spirituality and to facilitate more effective interventions.