Objective: This study was performed to evaluate the potential influence of cytological differences between pleural effusions on the survival of women with metastatic breast cancer during 30 months of follow-up. Study Design: A hospital-based cohort study was performed. Pleural fluid cytology slides from patients with breast cancer were examined. Cases were grouped according to the pattern of tumor cells (spheroid and isolated), in order to access their prognostic value. Results: The study comprised 87 patients. An isolated cell pattern was associated with higher mortality 30 months after the pleural effusion when compared to a spheroid pattern (p = 0.038). Patients with an isolated cell pattern showed higher risk of dying than patients with spheroid formations. The relative risk after adjustment of intervening variables was 5.336 (95% CI 1.054-27.020). The presence of a triple-negative immunohistochemical pattern significantly increased the risk of mortality before 30 months. Conclusion: Pleural effusion with isolated malignant cells is associated with worse prognosis after 30 months of follow-up.