Background. The diagnosis, treatment, and long-term management of cancer can present individuals with a multitude of stressors at various points in that trajectory. Psychosocial distress may appear early in the diagnostic process and have negative effects on compliance with treatment and subsequent quality of life.Purpose. The aim of the study was to determine early-phase predictors of distress before any medical treatment.Method. Consistent with the goals of the study, 123 newly diagnosed breast cancer patients (20 to 74 years old) completed multiple indicators of knowledge about breast cancer management and treatment, attitudes toward cancer, social support, coping efficacy, and distress.Results. SEM analysis confirmed the hypothesized model. Age was negatively associated with the patient’s knowledge (β = − 0.22), which, in turn, was positively associated with both attitudes toward breast cancer (β = 0.39) and coping self-efficacy (β = 0.36). Self-efficacy was then directly related to psychological distress (β = − 0.68).Conclusions. These findings establish indicators of distress in patients early in the cancer trajectory. From a practical perspective, our results have implications for screening for distress and for the development of early interventions that may be followed by healthcare professionals to reduce psychological distress.