This study aimed to explore the relationship between self-esteem and mental adjustment and examine the directional effects in patients with breast cancer using path modeling. This was a cross-sectional, descriptive, and correlational study. A total of 128 patients with breast cancer were selected through convenience sampling at a medical center in northern Taiwan. They completed a basic characteristics questionnaire, the Memorial Symptom Assessment Scale short form, the Rosenberg Self-Esteem Scale, and the mini-Mental Adjustment to Cancer Scale. Descriptive statistics, regression analysis, and path analysis were used to analyze the data. The results showed that higher self-esteem was associated with better mental adjustment (β = 0.9, 95% confidence interval 0.6~1.3, p < 0.001). Age, religious beliefs, employment, cancer stage, and symptom distress were correlated with mental adjustment. Path modeling demonstrated that self-esteem, cancer stage, performance status, and symptom distress directly affected mental adjustment in patients with breast cancer. These findings suggest that health professionals should evaluate self-esteem, performance status, and symptom distress in patients with breast cancer immediately upon admission. This can facilitate early implementation of relevant nursing interventions and, consequently, improve self-esteem and symptom distress and increase mental adjustment in these patients.