Purpose Significant cancer-related distress affects 30-60% of women diagnosed with breast cancer. Fewer than 30% of distressed patients receive psychosocial care. Unaddressed distress is associated with poor treatment adherence, reduced quality of life, and increased healthcare costs. This study aimed to evaluate the preliminary efficacy of a new web-based, psychoeducational distress self-management program, CaringGuidance™ After Breast Cancer Diagnosis, on newly diagnosed women's reported distress.Methods One-hundred women, in five states, diagnosed with breast cancer within the prior 3 months, were randomized to 12 weeks of independent use of CaringGuidance™ plus usual care or usual care alone. The primary multidimensional outcome, distress, was measured with the Distress Thermometer (DT), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Impact of Events Scale (IES) at baseline and months 1, 2, and 3. Intervention usage was continually monitored by the data analytic system imbedded within CaringGuidance™. Results Although multilevel models showed no significant overall effects, post hoc analysis showed significant group differences in slopes occurring between study months 2 and 3 on distress (F(1,70) = 4.91, p = .03, η 2 = .065) measured by the DT, and depressive symptoms (F(1, 76) = 4.25, p = .043, η 2 = .053) favoring the intervention. Conclusions Results provide preliminary support for the potential efficacy of CaringGuidance™ plus usual care over usual care alone on distress in women newly diagnosed with breast cancer. This analysis supports and informs future study of this selfmanagement program aimed at filling gaps in clinical distress management.